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Full text of "Annual Report of International Activities 1982"

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Prepared by 
John E. Fogarty International Center 

for 

Advanced Study in the 

Health Sciences 



U.S. DEPARTMENT OF 

HEALTH AND HUMAN SERVICES 

Public Health Service 

National Institutes of Health 

NIH PubUcation No. 83-62 
July 1983 





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Foreword 



On behalf of the National Institutes of Health 
(NIH), the John E. Fogarty International Center 
for Advanced Study in the Health Sciences (FIC) 
is pleased to present this I'tth Annual Report of 
International Activities , covering the fiscal year 
1982. Edited by the FIC, but based upon reports 
by each of the Bureaus, Institutes, and Divisions 
(bid's) of the NIH, this report provides an over- 
view of international activities for the period. 
These activities are essential to the furtherance 
of the NIH mission and fall within the purview of 
one or more of the BID's. 

The international programs of the NIH are 
specifically authorized under the International 
Health Research Act of 1960 (P.L. 86-610) to 
"advance the status of the health sciences in the 
United States and thereby the health of the 
American People through cooperative endeavors 
with other countries in health research, research 
planning, and research training. . . . "The bene- 
fits of NIH international programs, however, 
extend far beyond our borders. Cooperative 
relationships that the BID's have established 
through their intramural and extramural pro- 
grams enable foreign biomedical and behavioral 
research scientists to collaborate with their U.S. 
counterparts to discover better means for 
treatment, control, and~ultimately~prevention 
of disease worldwide. 

In 1968, the Fogarty International Center was 
established as the focal point for the interna- 
tional work of the NIH. Although the number and 
kinds of international programs differ from 
Institute to Institute, the FIC is the only NIH 
component with an explicit international mis- 
sion, which includes NIH-wide coordination of 
activities relevant to this mission in addition to 
the conduct of specific international programs of 
its own. 

The international activities of the NIH serve 
many scientific purposes, dictated by the spe- 
cific objectives of the intramural and extramural 
programs of the categorical Institutes and the 
support and service Divisions. Implementation of 
these activities must in turn be responsive to and 
consistent with national and international pol- 
icies. FIC coordinative functions link the NIH 
with other components of the Department of 
Health and Human Services, the Department of 
State, the Immigration and Naturalization 



Service of the Department of Justice, the U.S. 
Information Agency, foreign embassies in this 
country, science attaches, and multilateral 
organizations such as the World Health Organi- 
zation (WHO) and the Pan American Health 
Organization (PAHO). At the same time, inter- 
national activities from year to year reflect 
changes in the health scene as advances are 
made and new challenges emerge. The NIH also 
recognizes the important needs of developing 
nations and has fostered contacts that are 
described in this report. 

In its coordinative functions, the FIC has 
relied upon the cooperation of the BID's in 
providing the information for this report. To- 
gether we hope that the material is selected and 
presented in a way that is useful to a wide 
audience—including officials and the scientific 
community here and abroad—and illustrates the 
many ways international programs and activities 
contribute to biomedical and behavioral research 
and national health not only for the United 
States but also for the world at large. In assem- 
bling the overall report, we have made certain 
editorial modifications to the reports submitted 
by the individual BID's to achieve a consistent 
format. Because of size limitations, some dele- 
tions have been necessary. However, care has 
been taken not to alter the scientific content. 

The first chapter of the report presents high- 
lights of international activities that are de- 
scribed in greater detail in the individual BID 
chapters. In Chapter II, "Highlights of Recent 
Scientific Advances," we have chosen to empha- 
size two types of international research activ- 
ities: international biomedical collaboration 
(between U.S. and foreign scientists) and re- 
search in which foreign locations or population 
groups are important to the furtherance of 
scientific knowledge. Chapter III, prepared by 
the Office of the Director, FIC, describes 
activities and accomplishments of the programs 
conducted by the Center, as well as its coor- 
dinative and administrative functions. Subse- 
quent chapters discuss international programs 
and accomplishments of the individual BID's. 
Tables and figures summarizing NIH interna- 
tional activities in FY 1982 are appended. 

In contrast to the previous report, there is no 
separate chapter on activities with individual 



111 



countries. Rather, we have provided two indexes: of interest and use to a variety of audiences, and 

one that refers to descriptions of activities with we welcome comments that will enable us to 

individual countries and one that permits loca- achieve more fully this objective for future 

tion of material on specific diseases, conditions, reports, 
and research areas. 

Within the limitations of a single report it is Mark S. Beaubien, M.D. 

difficult to summarize the complex nature of Acting Director 

NIH international activities and their contribu- Fogarty International Center and 

tions to betterment of health in the United Acting Associate Director for 

States and abroad. Nevertheless, in this docu- International Research 

ment we have attempted to provide information National Institutes of Health 



IV 



Contents 



page 

Foreword iii 

I Overview of International Activities 1 

II Highlights of Recent Scientific Advances 3 

Components of the National Institutes of Health 9 

III John E. Fogarty International Center for Advanced Study in the Health Sciences 11 

IV National Cancer Institute 28 

V National Heart, Lung, and Blood Institute k5 

VI National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases 61 

VII National Library of Medicine 66 

VIII National Institute on Aging , 70 

IX National Institute of Allergy and Infectious Diseases 73 

X National Institute of Child Health and Human Development 87 

XI National Institute of Dental Research 90 

XII National Institute of Environmental Health Sciences 93 

XIII National Eye Institute 99 

XIV National Institute of General Medical Sciences 103 

XV National Institute of Neurological and Communicative Disorders and Stroke 104 

XVI Warren G. Magnuson Clinical Center 107 

XVII Division of Computer Research and Technology 108 

XVIII Division of Research Resources 110 

XIX Division of Research Services 112 

Appendix 115 

Index by Country 128 

Index by Research Area 129 



Tables and Figures 

Table page 

3-1. Scholars-in-Residence, 1982 1^ 

^-5. Countries/areas of origin of ICRETT awardees and their destinations, 1976-82 35 

4-2. The exchange of scientists under NCI's bilateral agreements programs 36 

4-3. Patient data, by cancer site and collaborating institute, entered into the ICPDES system . . 38 

4-4. International cancer research technology transfer 40 

4-5. Countries/areas of origin of ICRETT awardees and their destinations, 1976-82 41 

4-6. The NCI-PAHO collaborative cancer treatment research program by number of protocols 

and patient accrual 42 

4-7. NCI-PAHO collaborative cancer treatment research program by location and number of 

active protocols 44 

7-1. National Library of Medicine non-U. S. MEDLARS Centers 67 

A-1. Total expenditures for NIH international programs, by activity and BID, FY 1982 120 

A-2. NIH international research and research training awards by country /area and mechanism, 

FY 1982 122 

A-3. NIH international research and research training awards, FY 1947-82 126 

Figure 

1. NIH Organization Chart 10 

A-1. NIH international activities, funding by mechanism, FY 1982 117 

A-2. NIH international research and research training awards, FY 1973-82 118 

A-3. NIH international research and research training awards, FY 1973-82 119 



Vi 



Chapter I 



Overview of International Activities 



International activities relevant to the mis- 
sions of the Bureaus, Institutes, and Divisions 
(bid's) are described in their separate chapters. 
This chapter highlights features of these activ- 
ities that overarch the special roles of the NIH 
components, those that involve other agencies in 
the Public Health Service (PHS), other executive 
departments (e.g., Department of State), and 
such multilateral organizations as the World 
Health Organization (WHO) and the Pan Ameri- 
can Health Organization (PAHO). 

The breadth and complexity of NIH interna- 
tional activities are clearly illustrated in the 
sections on bilateral agreements in the BID 
chapters of this report and especially in the 
section containing the report of the Fogarty 
International Center (FIC) that describes its 
international coordination and liaison activities. 
These agreements, which are links between 
foreign and U.S. Governments, are usually es- 
tablished through the Department of State. The 
biomedical programs may be part of broad sci- 
ence and technology agreements or of more 
specific health agreements. As of 1982, the NIH 
was participating in over 39 bilateral agreements 
involving 29 countries, the most recent additions 
being Kuwait and Nigeria (1981) and Finland 
(1982). Because numerous Institutes (in some 
instances as many as 9 or 10) and other PHS 
components participate in agreements with a 
given country, the liaison function of the FIC 
contributes to smooth coordination of complex 
relationships. The FIC may also initiate rela- 
tionships with countries (coordinated with the 
State Department) and may involve appropriate 
BID'S, depending on the nature of the scientific 
or disease area involved. The bilateral agree- 
ments have been of great value in reducing 
social and political barriers to scientific ex- 
changes, in capitalizing on unique features of 
local environments and resources, and in foster- 
ing collaborative undertakings with shared tech- 
nical and professional resources and shared costs. 

Another source of funds for collaborative 
efforts is the Special Foreign Currency (P.L. 
'tSO) Program. As discussed in more detail in the 
report on the FIC International Research and 
Awards Programs, this source of support is being 
replaced, in most cases, by matching funds. 
These funds are administered by joint boards 



established by the United States and the foreign 
country. The joint boards review and monitor 
individual projects of mutual interest. 

All categorical components of the NIH, as well 
as the FIC, work closely with multilateral organ- 
izations, especially the WHO. The FIC coordi- 
nates NIH advice for the Department of Health 
and Human Services (DHHS) and its represen- 
tation to the WHO concerning agenda, budget, 
and policy issues. 

During FY 1982, the FIC was designated as the 
first WHO Collaborating Center for Research 
and Training in Biomedicine. This designation, 
which is for a 'f-year period, provides a new kind 
of opportunity for the United States (via the 
NIH) to expand its leadership role in interna- 
tional biomedical sciences. Activities in the 
planning stage include expanded information 
exchange and strengthened linkages with coun- 
terpart research organizations in other countries. 

An objective measure of other NIH coopera- 
tion with WHO is the number of other BID's that 
serve as WHO Collaborating Centers: 

• The National Cancer Institute (NCI) is a 
Collaborating Center for Reference on 
Tumors of Laboratory Animals. 

• The National Heart, Lung, and Blood In- 
stitute (NHLBI) is a Collaborating Center 
for Research and Training in Cardiovascular 
Diseases for the Americas. 

• The National Institute on Aging (NIA) is a 
Collaborating Center for Joint Cooperation 
on Research on-Care of the Aged. 

• The National Institute of Allergy and In- 
fectious Diseases (NIAID) is a Collaborating 
Center for Rickettsial Reference and Re- 
search, Mycoplasma Reference and Re- 
search, Virus Reference and Research, and 
Interferon. 

• The National Institute of Dental Research 
(NIDR) is a Collaborating Center for Re- 
search in the Prevention of Dental Caries 
and Periodontal Diseases. 

• The National Institute of Environmental 



Health Sciences (NIEHS) is a Collaborating 
Center for Environmental Health Effects. 

• The National Eye Institute (NEI) is a Col- 
laborating Center for the Prevention of 
Blindness. 

• The National Institute of Neurological and 
Communicative Disorders and Stroke 
(NINCDS) is a Collaborating Center for 
Research and Training in Neurosciences. 

• The Division of Research Resources (DRR) 
is a Collaborating Center for Reference and 
Research in Simian Viruses. 

• The Division of Research Services (DRS) is a 
Collaborating Center for Defined Labora- 
tory Animals. 

The intramural NIH scientists have been a 
valuable resource to the FIC, bringing their 
expertise to bear when serving as nominators and 
reviewers of Scholars-in-Residence, as members 
of the Scholars-in-Residence Advisory Panel, or 
as members of the FIC secondary review group 
for Senior International Fellowships, Interna- 
tional Research Fellowships, or International 
Conference Awards. In turn, the FIC contributes 
to the intramural programs of the NIH Institutes 
through its Foreign Scientists Assistance Pro- 
grams, which provide coordination, guidance, and 
assistance to the BID scientific directors and to 
the foreign scientists who are invited to the NIH 
as Visiting Fellows, Visiting Associates, Visiting 
Scientists, or Guest Researchers. In FY 1982 this 
activity involved over 1,^00 scientists from over 
60 countries. 

Through the International Issues Study-Pro- 
gram, the FIC also involves appropriate BID 
scientists in studies by special task forces of 
selected topics of international relevance. 

More specific accomplishments under each of 
these programs are described in the chapter on 
the programs of the FIC. 

The scientific community at the NIH and that 
supported by the NIH through its extramural 
programs have extensive relationships with over 
60 countries worldwide. Selected scientific high- 
lights of these activities are reported in the next 
chapter. 

Tabular and graphic summaries of NIH inter- 
national actvities are presented in the appendix. 
In FY 1982, $62 million of NIH's total appropri- 
ation of $3.6 billion was devoted to international 
activities (see table 1, Appendix). This consti- 
tutes about 1.6 percent of the NIH appropriation. 
This proportion has remained stable in recent 
years. Of this $62 million, about $21 million, or 
3^^ percent, supported scientist exchanges: for- 
eign scientists conducting collaborative research 
in the United States and U.S. scientists con- 
ducting research abroad ($15.7 million of this 



amount was devoted to the support of foreign 
visiting scientists who conduct collaborative 
research with intramural scientists at the NIH). 
Another $11.^^ million, or 22 percent of the 
amount spent on NIH international activities in 
FY 1982, was devoted to support of research 
grants held by foreign investigators. These 
awards have been reviewed for scientific excel- 
lence, for BID program relevance and priority, 
and for assurance that performance in a foreign 
country would yield a particular value. About 
$12 million, another 17 percent, was used to 
support foreign contracts that are awarded only 
after competitive peer review and justification 
for the conduct of the research in the foreign 
country. The remainder supported international 
conferences, travel, and bilateral and staff ex- 
changes. Almost half of the $62 million devoted 
to international programs was actually expended 
in the United States on activities including sup- 
port for foreign scientists and Fogarty Scholars 
who study in the United States, travel, and bi- 
lateral exchanges to the United States of foreign 
scientists. Appendix figure 1 depicts these 
activities by broad categories of program mech- 
anisms. 

Appendix table 2 displays the FY 1982 expend- 
itures for research and research training awards, 
by country or area and type of award. Most of 
the foreign grants and contracts were awarded 
to scientists in Canada ~ $7.^ million ~ with 
scientists from Israel receiving awards in the 
amount of $^A million; those from the United 
Kingdom, $3.5 million; and those from Japan, 
$3.^ million. Australia, Brazil, Egypt, India, 
Italy, and Sweden were awarded totals of $1 mil- 
lion to $3 million. 

International organizations including WHO, 
PAHO, and the International Agency for Re- 
search on Cancer (lARC) were awarded about 
$3.7 million in grants or contracts in FY 1982. 

Appendix table 3 provides information on 
trends of NIH international research and re- 
search training awards. These activities reached 
a level of $^^9 million in FY 1982. These amounts 
include the $1.^ million in awards made from 
Special Foreign Currency (P.L. ^80) money. This 
money is appropriated to the Office of the 
Assistant Secretary for Health, DHHS, and is 
reviewed and administered by the NIH. 

Over the past 10 years, Visiting Program sup- 
port and research grants to foreign scientists 
have increased to a greater extent than have 
other types of international activities. The 
amount devoted to international research con- 
tracts remains at about $11 million. These trends 
are depicted in figure 2 in the appendix. In terms 
of constant 1973 dollars, however, the amount 
devoted to international research and research 
training awards in FY 1982 was only slightly 
more ($23 million) than the FY 1973 amount of 
$19.6 million. These trends are depicted in figure 
3 in the appendix. 



Chapter H 
Highlights of Recent Scientific Advances 



The following highlights present a selective 
summary of scientific activities and accom- 
plishments under international research pro- 
grams sponsored by the Bureaus, Institutes, and 
Divisions of the NIH. Drawing upon detailed 
reports submitted by the BID's, this chapter 
places the activities and accomplishments in the 
context of global health problems and illustrates 
the benefits of international collaboration in 
biomedical research. Some studies between the 
United States and other countries are reported 
here because they employ innovative research 
approaches or new technologies or examine 
special populations, even though the projects are 
in the early stages. They are relevant because 
they are opening new paths to the solution of 
health problems of international concern. 

Two types of projects have been selected for 
special reporting here: first, collaborative bio- 
medical projects in which scientists from the 
United States and at least one other country 
participate to develop new knowledge that will 
lead to the prevention or alleviation of diseases 
or afflictive conditions; and second, epidemio- 
logical studies, in which scientists, working 
collaboratively, take advantage of the availa- 
bility of specific cultural settings and environ- 
ments in various parts of the world. These groups 
have often been valuable resources for the study 
of disease prevention and disease control using 
epidemiologic methods of investigation. Through 
their international research programs, the In- 
stitutes of NIH have engaged in cooperative 
epidemiologic studies with foreign countries 
when particular features were eminently suitable 
for learning about factors that cause or influ- 
ence the course of a disease. In some instances, 
a population has been exposed to environmental 
factors rarely found elsewhere, or a group with a 
common genetic background provides enough 
individuals with a genetically determined disease 
to be suitable for an epidemiologic study. In still 
other instances, studies drawing on an ethnic 
background make it possible to trace the influ- 
ence of such factors as dietary habits, behavior 
patterns, and lifestyles on the incidence and 
prevalence of a disease. 

Recent accomplishments and ongoing projects 
of these two types of activities are described 
below. 



International Collaborative Projects to 
Prevent or Alleviate Disease 



Collaborative research between NCI scientists 
and those of China on the biochemical epidemi- 
ology of cancer of the esophagus has revealed 
that in Linxian Province staple food is heavily 
contaminated by a Fusarium genus. They have 
found that T2 toxin produced by Fusarium has 
both direct cytotoxic and proliferative effects 
on fetal esophageal epithelium. At high dosage 
of the toxin, cultured epithelial cells became 
necrotic, whereas at lower doses the toxin 
caused mitogenic effects including focal basal 
cell hyperplasia, dysplasia, and increased num- 
bers of mitoses. Atypical mitoses were also 
observed. These changes are very similar to the 
premalignant lesions seen in epithelium adjacent 
to human esophageal carcinoma. The lead es- 
tablished in China on the possible role of a fun- 
gal mycotoxin in human esophageal carcino- 
genesis is being pursued in a quantitative way. 

By virtue of the agreement between the NCI 
and the Japanese Society for the Promotion of 
Science, teams of American and Japanese vir- 
ologists independently isolated and identified 
retroviruses that are associated with a human T 
cell leukemia virus (HTLV) and the adult T cell 
leukemia virus (ATLV), respectively. These are 
newly identified human retroviruses, which seem 
to be identical or very similar to each other. The 
viruses are closely associated with mycosis fun- 
goides, Sezary syndrome, and adult T cell leu- 
kemia, which belong to the category of differ- 
entiated T cell lymphoma and leukemia. The 
viruses have been found to be endemic in the 
southwestern part of Japan and certain Carib- 
bean Islands. 

During his sojourn in the Institute of Oncology 
in Warsaw, Poland, an American pharmaceutical 
chemist collaborated with Polish counterparts on 
the synthesis and quality-control testing of P-32 
labeled ion exchange resin microspheres for 
radiation therapy of hepatic neoplasms. Repre- 
sentative samples of the microspheres were 
injected intraperitoneally into rats. Because of 
the low uptake of the radioactive microspheres 
by the liver following intraperitoneal injection, a 



new approach was adapted for administration of 
the microspheres. Increased absorption of the 
radioactive agent occurred after delivery via a 
catheter inserted into the hepatic artery. In- 
formation gained from trials in experimental 
animals is expected to show that a larger number 
of the smaller microspheres will deliver a radi- 
ation dose more exactly matching the distri- 
bution of capillary blood flow. It is believed that 
the radiation therapy from the beta decay of 
P-32 microspheres, when combined with surgery 
and/or chemotherapy, will result in a better and 
longer life for the cancer patient. 

A visiting Hungarian scientist, working with 
his American counterpart at the Roswell Park 
Memorial Institute, studied methods of tumor 
cell disaggregation—mechanical and enzymic— 
for yielding single cell suspensions. Among 17 
tumors studied, the number of cells obtained by 
disaggregation differed widely. Considering the 
disaggregated samples as the starting material, 
researchers found the recovery rate ranged from 
30.7 to 82 percent, with a mean value of 49 
percent and 56.3 percent, respectively, for 
mechanically and enzymically disaggregated 
samples. A high degree of separation of tumor 
cells from leukocytes and red blood cells occur- 
red, the separation of macrophages from tumor 
cells being more difficult. Intracellular concen- 
tration of the anticancer agent Ara-C and ^H- 
thymidine was higher in the fractions with more 
viable cells. The effect of another anticancer 
agent, DDP, was opposite in that the results 
suggest an intensive binding to nonviable cells. 
Thus, it seems important to separate more 
clearly the viable and nonviable cells to deter- 
mine whether the reduced or increased uptake of 
precursor or drug in nonviable cells is due to 
metabolic failure or whether the nonviable cells 
represent a metabolically distinct population 
with preserved growth potential. 

Ten American cancer centers and 13 cancer 
institutes in Latin America are participating in 
the Collaborative Cancer Treatment Research 
Program (CCTRP) established between the NCI 
and PAHO, where 26 active cancer treatment 
protocols are now being investigated. Over the 
total life of the program as many as 37 protocols 
have been active in a single year. Eleven proto- 
cols have been completed or terminated. 

During the 4 years that this program has been 
in full operation, 2,342 patients have been ac- 
crued in the various protocols. An effective 
international collaborative research program, 
the CCTRP shows itself an excellent medium for 
(1) promoting and practicing, at the interna- 
tional level, the concept that clinical research is 
the best means to prove the effectiveness of a 
given treatment; (2) identifying the most satis- 
factory techniques for a given trial and promot- 
ing their standardized use; (3) accelerating re- 
sults by pooling efforts and resources; (4) stim- 
ulating the design of innovative studies attempt- 



ing to solve questions of local as well as of 
international interest; and (5) opening channels 
of communication for the exchange of new ideas 
and the comparison of results from institutional 
and individual accomplishments. 

As a result of exchanges between American 
hosts and two visiting Soviet chemotherapists, a 
protocol was drafted for a Phase I Clinical and 
Pharmacologic Trial of Platinumdiammine 
(CBDCA). The joint study is underway as a col- 
laborative effort between the University of 
Maryland Cancer Center and the All-Union On- 
cologic Scientific Center in Moscow. Paralleling 
the studies being pursued in the United States, 
the Soviet effort includes (1) establishing the 
maximum tolerable dose of CBDCA in cancer 
patients; (2) evaluating CBDCA toxicity in pa- 
tients with previously treated and untreated 
malignancies; (3) determining the antitumor 
activity of CBDCA; and (4) determining the clin- 
ical pharmacokinetics of the anticancer agent. 

Significant progress has been made in the 
collaborative studies of the biochemical epi- 
demiology of human esophageal and liver cancers 
by American and Chinese scientists. Methods to 
culture human esophageal and liver tissues have 
been established in China. From experimental 
studies, it has been determined that these tis- 
sues, in culture, retain the capacity to activate 
aflatoxin Bj, benzo(a)pyrene, and N-nitrosodi- 
ethylamine. These and other carcinogen-DNA 
adducts have been identified by high-pressure 
liquid chromatography. Progress is being made as 
well in establishing the conditions to culture 
monolayers of human hepatic and esophageal 
epithelial cells. 

Collaborative research has been conducted 
with personnel of the Cairo Cancer Institute 
through a formal bilateral agreement with 
Egypt. Recently, a Phase II study of chemother- 
apeutic agents, initiated in 1976, was completed. 
Twelve drugs were studied in about 400 patients 
with squamous and transitional cell bilharzial 
bladder carcinoma. The drugs included hexa- 
methylmelamine, VM26, methotrexate, bleo- 
mycin, adriamycin, platinum, Cytoxan, 5-fluor- 
ouracil, trenimone, m-AMSA, vincristine, and 
pentamethylmelamine. Notable response rates 
were seen with hexamethylmelamine, penta- 
methylmelamine, vincristine, and trenimone. On 
the basis of these results, an active chemother- 
apy combination might include vincristine, 
pentamethylmelamine, and 5-fluorouracil. The 
durable response rate after radical cystectomy 
in bilharzial bladder carcinoma is 35 percent 
(5-year disease-free survival), which is not im- 
proved by pre- or postoperative radiotherapy. 
Thus, initiation of a controlled trial of radical 
cystectomy plus or minus adjuvant chemotherapy 
is timely. The combination described is under 
active consideration, as are other combinations. 

During the course of U. S. - U. S. S. R. col- 
laboration under the bilateral agreement in the 



cardiovascular area, scientific progress has been 
made on a number of topics. This year the tar- 
geting of drugs to injured heart muscle has re- 
ceived special attention. 

Soviet scientists have developed synthetic 
liposomes, a microscopic colloidal fat particle, 
suitable for injection. In recent years, research- 
ers have recognized liposomes as promising 
carriers for drug transport in vivo. However, the 
relatively rapid clearance of the liposomes, 
which results from their capture by cells of the 
reticuloendothelial system primarily in the liver, 
still limited their everyday clinical use. A Soviet 
investigator working with a U.S. colleague has 
now succeeded in linking antibodies specific for 
cardiac myosin to liposomes. When cardiac mus- 
cle is damaged by lack of oxygen, unique intra- 
cellular antigens are uncovered, which are rec- 
ognized by this liposome-antibody complex. An 
antibody-antigen interaction occurs that binds 
the liposomes to the damaged cardiac muscle. By 
adding an isotopic marker to the drug liposome 
complex, scientists can visualize the damaged 
muscle simultaneously as the therapeutic agent 
is rapidly and preferentially applied to it. The 
binding of the liposomes to the cardiac muscle 
also slows their excretion, thereby prolonging 
the efficacy of action of the drug that they are 
transporting. 

Sickle cell anemia is a hereditary disease that 
affects 50,000 black Americans and perhaps 2 
million people worldwide, mostly in Africa. This 
condition results from an abnormal hemoglobin, 
called hemoglobin S, which polymerizes or ag- 
gregates upon deoxygenation and distorts the 
blood's red cells into an elongated, sickle-like 
shape. Recent research indicates that the in- 
flexibility inherent in such "sickled" cells (not 
the shape per se) leads to the tissue damage and 
destruction of red blood cells that is charac- 
teristic of this severe, and even fatal, disease. 

Intramural scientists at the National Institute 
of Arthritis, Diabetes, and Digestive and Kidney 
Diseases (NIADDK) have conducted extensive 
investigations into the polymerization process 
that characterizes hemoglobin cells in sickle cell 
anemia. 

In the search for a therapy for this disease, 
recent collaboration between investigators in 
NIADDK's Laboratory of Chemical Biology and 
foreign investigators has been particularly help- 
ful. For instance, a Fogarty Scholar-in-Resi- 
dence from Japan has provided singular ingenuity 
in suggesting the synthesis of individual peptides 
that might block the gelation (polymerization) of 
hemoglobins. In another instance, collaboration 
with a British scientist may lead to discovery of 
the mechanism whereby certain peptides can 
inhibit the gelation of hemoglobin. 

This research could ultimately result in a 
rational and effective therapy for sickle cell 
anemia, both in the United States and in Africa, 
and could provide an outstanding example of the 



cross-fertilization that often evolves from in- 
ternational scientific collaboration. 



International Collaborative Projects to 
Study Disease Etiology and Identify 

Risk Factors 

Increasingly, investigators are convinced that 
to prevent or minimize the adverse effects of 
environmental factors, adequate methodologies 
to predict the toxicity of these environmental 
factors must be developed. NIEHS scientists, 
through multilateral and bilateral agreements in 
collaboration with scientists throughout the 
world, have played a leading role in assessing 
current methods and developing better method- 
ologies for assessing the toxic potential of en- 
vironmental chemicals. Major emphasis has been 
placed on international collaboration aimed at 
developing better short-term methods for de- 
tecting whether chemicals can cause such toxic 
effects as genetic mutations, birth defects, and 
damage to various organ systems. For example, 
recent remarkable advances in the fields of 
genetics and mutagenesis have revolutionized 
the fields of toxicology and carcinogenesis by 
providing new short-term test methods to reveal 
whether chemical substances can damage DNA. 
Detection of damage to DNA has important 
implications for carcinogenesis and heritable 
genetic diseases. Clearly, a number of factors 
interact to determine the ultimate action of 
chemical mutagens and carcinogens. Under the 
U.S.-3apan Cooperative Medical Sciences Pro- 
gram, Japanese and American scientists have 
successfully identified dietary factors capable of 
enhancing or inhibiting the mutagenic activity of 
substances found in food. For example, muta- 
genic and carcinogenic compounds from broiled 
fish and ground beef have been isolated and 
identified. Additional tests are being conducted 
with a variety of other foods that can reduce the 
activity of the mutagens in cooked meats. These 
studies may eventually lead to the prevention of 
cancer and genetic diseases in which diet is a 
contributing factor. 

Exposure to physical environmental factors 
has also become of growing concern as the num- 
ber of emission sources has increased. Under the 
U.S.-U.S.S.R. Medical Science and Public Health 
Agreement, joint studies on the biological ef- 
fects of microwave radiation, and static and low 
frequency electromagnetic fields are underway. 
Now that a detailed protocol for a duplicate 
experiment has been developed, both sides will 
compare the same behavioral, electrophysio- 
logical, and biochemical methods under exposure 
conditions as identical as possible. The purpose is 
to determine, first, whether both groups will 



observe the same effects and, second, which 
methods appear to be the most sensitive. It is 
hoped that this study will provide insights into 
the reasons why Soviet scientists generally re- 
port effects of electromagnetic waves on the 
nervous system at exposure levels below those 
reported in the United States. 

The impact of migration on cardiovascular 
disease is an important public health concern. 
After studying variations in motivations and 
personal characteristics of migrants and nonmi- 
grants, scientists have discovered significant 
differences in disease patterns. Filipino mi- 
grants, for instance, experience higher risk of 
hypertension and death due to cardiovascular 
disease after migration to Hawaii or California. 
Similar increases were reported for Japanese 
migrants to these areas. Although hypertension 
is a major health problem in both Asians and 
Europeans, in Asians the most prevalent sequela 
is stroke, while in Europeans heart attack is the 
most frequent outcome. The changing risk ex- 
perienced by Asian migrants to westernized 
areas indicates a large environmental factor in 
the etiology of cardiovascular disease. Yet, the 
process of westernization has resulted in con- 
flicting patterns of cardiovascular disease in 
different countries. In the Philippines this proc- 
ess, which includes a Western diet, is accompan- 
ied by an increased risk of coronary heart dis- 
ease, while in Japan coronary heart disease is 
decreasing in spite of westernization and in- 
creased consumption of saturated fats. Examin- 
ation of these differences may uncover clues to 
the relative importance of the various known 
risk factors in the etiology of cardiovascular 
disease. More important, it may lead to further 
decrease in cardiovascular disease through a 
lessening or elimination of these risk factors. 

An extremely high incidence of Huntington's 
disease (HD) exists among certain residents 
around Lake Maracaibo in Venezuela, all report- 
edly descended from a Spanish sailor who arrived 
in the country in 1860. Scientists at the Univer- 
sity of Zulia in Maracaibo are working with 
NINCDS scientists and grantees on a study of 
over 200 HD patients in the area and 2,000 of 
their relatives. 

Since these Venezuelans have all inherited an 
identical HD gene, they are particularly valuable 
subjects for research. In addition, several fami- 
lies have intermarried, creating the possibility 
that some descendants may carry two genes for 
HD. These features make this community unique 
in the world. No one knows whether such a 
"double dose" of the gene would be lethal to the 
fetus or would greatly shorten the life of any 
child born alive; however, if individuals carrying 
two genes for HD can be found, they would be 
ideal subjects for studying the precise metabolic 
abnormality arising from the defective gene. 

In 1981 and 1982, the NINCDS conducted two 
scientific expeditions in Venezuela. Venezuelan 



HD patients and at-risk family members were 
examined neurologically and psychologically, 
were filmed to document clinical status, and 
were administered medical history question- 
naires. Blood and skin samples have been taken 
from over 260 patients, family members, and 
controls and have been sent to NINCDS grantees 
for analysis. The Venezuelan pedigrees collected 
so far have been computerized and are now part 
of an NINCDS-supported Huntington's Disease 
Research Roster at the University of Indiana. 

Grantees using the Venezuelan cell lines are 
generating "maps" identifying the location of the 
patients' genes on the chromosomes. These maps 
will be useful for locating any defective gene 
causing inherited disease, as well as for under- 
standing normal inheritance. This research, on 
the forefront of neurogenetic investigations, 
holds tremendous promise, not only for con- 
trolling Huntington's disease, but also for al- 
leviating suffering worldwide. 

In FY 1982, the NINCDS continued to expand 
its program in neuroepidemiology, a major por- 
tion of which entails collaboration with sci- 
entists and health workers in other countries. 

The failure of governments and health agen- 
cies in most developing countries to measure 
accurately the extent of various disorders cre- 
ates a serious problem. Many have few resources 
for such measurement and no usable data. To 
begin to meet this need, the NINCDS and WHO 
have developed a screening examination and 
questionnaire that can be used by lay health 
workers and have joined with health officials to 
pilot test the examination and questionnaire in 
Nigeria, Mexico, and China. The examination and 
questionnaire are designed specifically to find 
cases of cerebrovascular disease, epilepsy, ex- 
trapyramidal disorders, brain tumors, peripheral 
neuropathies, and migraine headache. They are 
also designed to facilitate statistical compari- 
sons among countries. Two interesting prelimi- 
nary findings have come from the early data: 
rural Nigerian populations have a prevalence of 
migraine headaches similar to residents of major 
U.S. and European cities; and China has the 
highest prevalence of cerebrovascular disease of 
any country in the world where the problem has 
been studied. The NINCDS, WHO, and officials in 
China, Nigeria, and Mexico are now planning the 
project's second phase, which will study possible 
risk factors. A third and final phase should de- 
termine the best methods of control and pre- 
vention. 

A number of other countries— including Peru, 
Colombia, Venezuela, Kenya, India, and Sene- 
gal—are adapting the questionnaire and exami- 
nation for their own purposes. 

The NIA, still in the first decade of develop- 
ment, continues to participate in activities that 
promote general scientific cooperation among 
national institutes and programs of gerontology 
around the world. Outstanding research projects 



of high scientific merit that are particularly 
relevant to NIA programs are in some cases 
more directly supported by the Institute. 

One such example is a collaborative project 
the Institute has developed with a French expert 
on studies relating to dihydroepiandrosterone 
(DHEA). Worldwide interest in this naturally 
occurring hormone is increasing, because the 
DHEA level decreases with age and abnormal 
levels are observed in many pathological states. 
Research results and theoretical interpretations 
of these results vary considerably and tend to be 
quite controversial. 

Because it is important to understand the 
relationship of this hormone to the aging proc- 
ess, the NIA Biomedical Research and Clinical 
Medicine Program has entered into a cooperative 
arrangement with a well-known investigator 
from the University of Paris to examine natu- 
rcilly occurring levels of DHEA in the tissues of 
mice and rats supplied from NIA colonies of aged 
animals. These analyses are expected to yield 
important information to the NIA on the value of 
mice and rats as models for DHEA research and 
at the same time contribute to the investigator's 
DHEA research program in France. 

The populations in the Pacific region and the 
health impact of their migration to the United 
States offer a wide range of opportunities to 
extend our knowledge of how environmental and 
genetic factors interact to influence cardio- 
vascular disease patterns. In order to explore and 
evaluate these scientific opportunities, the 
NHLBI held an international workshop on the 
Changing Patterns in Cardiovascular Disease in 
the Pacific Basin, in January 1982. Data were 
presented from the following countries and re- 
gions: China, Taiwan, the Philippines, Australia, 
New Zealand, Micronesia, Hawaii, other islands 
of the South Pacific, and the WHO Region for 
the Western Pacific. The scientists recommend- 
ed that these unique opportunities for special- 
ized studies in the Pacific region be exploited to 
the utmost. To take advantage of already avail- 
able baseline information and disease prevalence 
data, investigators must complete incidence 
followup examinations in the Guam and Palau 
survey populations and the California cohort of 
the NI-HON-SAN Study (Japanese living in 
Japan, Hawaii, and California). Standardized 
surveillance of cardiovascular disease trends and 
risk factors needs to continue in Fiji, the Phil- 
ippine Islands, and several Pacific Island groups 
where cardiovascular disease and associated risk 
factors appear to be increasing. New insights 
into the relative roles of the environment and 
genetics in the etiology of cardiovascular disease 
may result from studies of the causes of urban- 
rural differences in the Philippines and Fiji and 
of serum cholesterol levels in Japan, the North- 
South differences in hypertension prevalence in 
China and Japan, the different coronary heart 
disease mortality rates among migrants and 



nonmigrants in Australia, and the different risk 
of cardiovascular disease among Indians and 
Fijians in Fiji. 

Because sudden infant death syndrome occurs 
primarily during sleep, a better understanding is 
needed of the effects of development on sleep 
cycles and of the interaction between the sleep 
cycle and respiratory activity. Studies underway 
in Australia using immature and adult marsupi- 
als, called potoroos, will help to determine de- 
velopmental characteristics of respiratory con- 
trol during sleep. Because marsupial offspring 
are born at a very early stage of development 
and continue developing in the marsupial pouch, 
this particular animal offers the unique advant- 
age of easy access to young mammals at stages 
corresponding to the fetal or intrauterine periods 
in other species. 

In the Dominican Republic, investigators sup- 
ported by the National Institute of Child Health 
and Human Development (NICHD) have been 
working with a pediatrician to study an unusual 
group of Dominican children who are born ge- 
netically male, but because of a congenital en- 
zyme deficiency (5-alpha-reductase), their ex- 
ternal genitals appear to be female. 

At the time of puberty, these children who 
have been raised as girls suddenly act like boys: 
a dramatic switch of gender role occurs even 
without phallic development. This complete 
sexual reversal clearly demonstrates that gender 
identity is not fixed in early childhood and that 
testosterone profoundly affects the brain at the 
time of puberty in establishing male identity and 
behavior patterns. These discoveries have im- 
portant implications for the therapy of children 
who are born with other kinds of sexually am- 
biguous genitalia. 

In Asia a cross-cultural study of the factors 
that determine the timing of first births has 
revealed the apparent universality of the effects 
of socioeconomic variables, such as education or 
rural/urban origins, on the timing. In Asian 
societies as dissimilar as Hong Kong and the 
Philippines, these variables have the same ef- 
fect; yet the importance of cultural heritage 
remains. 

After other factors are taken into account, 
the Confucian heritage groups have substantially 
later ages at first birth than the Muslim and 
Hindu groups, with substantially younger ages at 
first birth. The study also has shown that in- 
creases in age at marriage found in many de- 
veloping countries have not had so great an 
impact on reducing fertility as once thought. In 
general, the later the age at marriage, the 
sooner the first birth occurs and the higher the 
level of early marital fertility. 

Two researchers from Brock University in 
Canada have collaborated with the Physical 
Sciences Laboratory of the DCRT in studying the 
theory and measurement of intermolecular 
forces. This project has succeeded, for the first 



time, in directly measuring the force between distance, as well as elucidating the effect of 

biological macromolecules, providing a good structure on this force. An extension of the work 

picture of how the force between parallel DNA will allow the determination of important ther- 

helices behaves in response to changes in modynamic parameters of proteins. 



Compomnis 
ofHeMi 



Figure 1.— NIH organization chart 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES 
PUBLIC HEALTH SERVICE 
NATIONAL INSTITUTES OF HEALTH 



Deputy Director for 
Intramural Research 




/yyyyVy Associate Director for ^^TT/y^ 
yyyyyy; International Research /Vyyyy 
////////////////////////////A 


Deputy Director for Extramural 
Research and Training 








Associate Director for Program 
Planning and Evaluation 




Director 




Associate Director for Medical 
Applications of Research 


Associate Director for 
Administration 




Deputy Director 




Associate Director for 
Clinical Care 


Associate Director for 
Communications 










Assistant Director for 
Intramural Affairs 






Associate Director for 
Research Services 






' 





Bureaus 



National 
Cancer Institute 



National Heart, 

Lung, & Blood 

Institute 



National Institute of 

Arthritis, Diabetes, & 

Digestive & Kidney 

Diseases 



National Library 
of Medicine 



National Institutes 



Aging 



Allergy & 
Infectious Diseases 



Child Health & 
Human Development 



Environmental 
Health Sciences 



Eye 



General 
Medical Sciences 



Dental 
Research 



Neurological & 

Communicative 

Disorders & Stroke 



Research & Support Divisions 



Clinical 
Center 



Research 
Grants 



Computer Research 
& Technology 



Research 
Resources 




Research 
Services 



10 



Chapter HI 
John E. Fogarty International Center 
for Advanced Study in the Health Sciences 



Introduction 

The Fogarty International Center for Advanced 
Study in the Health Sciences (FIC) was created 
in 1968 to provide a focus and organizational 
mechanism for NIH activities in international 
biomedical research. The mission and objectives 
of the FIC are to: 

• Facilitate the assembly of scientists and 
leaders in the biomedical, behavioral, and 
related fields for discussion, study, and re- 
search relating to the development of sci- 
ence internationally as it pertains to health 
and its implications and applications for the 
future; 

• Further international cooperation and col- 
laboration in the life sciences through its 
research programs, conferences, and 
seminars; 

• Provide postdoctorate fellowships for 
training in the United States and abroad and 
promote senior scientist exchanges between 
the United States and other countries; 

• Coordinate NIH activities and functions 
generally concerned with health sciences at 
an international level; and 

• Serve as a focal point for foreign visitors to 
the National Institutes of Health. 

The Director, FIC, is also the NIH Associate 
Director for International Research, in which 
capacity he advises the Director of the NIH on 
the development of international policies and 
procedures related to health. On international 
issues the FIC interacts with each of the BID's 
of the NIH, as well as with other components of 
the Department of Health and Human Services. 
In addition, the FIC maintains liaison with the 
Department of State and other Government 
agencies, with foreign embassies, and with mul- 
tinational and foreign organizations. 

The FIC discharges its responsibilities through 
four program activities: Advanced International 



Studies, Foreign Scientists Assistance, Interna- 
tional Research and Awards, and International 
Coordination and Liaison. The FIC also provides 
core support for the Gorgas Memorial Labora- 
tory in Panama. 

During FY 1982, the FIC was designated as the 
first WHO Collaborating Center for Research 
and Training in Biomedicine for a l^-year period. 
The FIC has begun to fulfill its role as a WHO 
Collaborating Center by expanding its informa- 
tion exchange activities and linkages with coun- 
terpart research organizations in other countries. 

Additional FIC program highlights during FY 
1982 were the initiation of a Nominating Com- 
mittee for the International Research Fellowship 
(IRF) Program in China, the reactivation of the 
IRF Nominating Committee in the West Indies, 
and the negotiation of an agreement between the 
FIC and the Alexander von Humboldt Foundation 
in the Federal Republic of Germany for the FIC 
to announce the availability of German fellow- 
ships for U.S. scientists. 

Specific program activities and accomplish- 
ments are presented in the following sections. 

Advanced International Studies 

The goal of Advanced International Studies 
Programs is to facilitate international scientific 
communications by providing international for- 
ums for the exchange of scientific information 
and for the review and evaluation of major areas 
of biomedical research, particularly as related to 
international health problems of mission interest 
to the National Institutes of Health. 

Advanced international studies in the health 
sciences are aided through three FIC inter- 
related programs: International Issues Study- 
Program, International Conferences and Semi- 
nars Program, and Scholars-in-Residence Pro- 
gram. The fundamental purpose of these pro- 
grams is to review and evaluate recent research 
results and the derivative knowledge so that the 
best directions for further scientific research to 
overcome or avoid major health problems will be 
apparent. These activities tap scientific talent, 
not only throughout the United States, but also 



11 



in any country in the world where it exists. The 
major goal of these programs is to evaluate and 
transfer new knowledge and technologies to or- 
ganizations and individuals to whom the new 
information will be useful. 



International Issues Study-Program 

This program effort is devoted to harnessing 
the best pertinent health science talent in the 
world to analyze major health problems of mul- 
ticountry interest and to give advice and guid- 
ance to national health authorities on actions to 
be taken, individually and collectively, to over- 
come the problems. Issues addressed include in- 
ternational aspects of biomedical and behavioral 
research, research manpower training, and the 
transfer of research results to bring new know- 
ledge to bear where it will benefit health 
worldwide. 

Identification of aspects of the problem cal- 
ling for further research is of paramount interest 
in each project. Some projects are described 
below. 

International Conference on the Eradication of 
Infectious Diseases 

Published in the Sept.-Oct. 1982 (Vol. ^, No. 5) 
issue of Reviews of Infectious Diseases were the 
proceedings of the International Conference on 
the Eradication of Infectious Diseases, con- 
ducted by the FIC and a number of other agen- 
cies in May 1980. At that conference the par- 
ticipants analyzed the nature of the program 
activities that led to the world eradication of 
smallpox. With those procedures in mind, they 
then determined their applicability to other in- 
fectious diseases. Among the recommendations 
stemming from that evaluation were separate, 
indepth analyses of measles, poliomyelitis, and 
yaws. The FIC has moved to accomplish these 
analyses, each with the relevant national and 
international health-related agencies. 

International Symposium on Measles 
Immunization 

Conducted in March 1982, this international 
symposium accommodated the enthusiastic par- 
ticipation of scientists from many parts of the 
world. During the assessment of the current im- 
pact of measles on the world population, par- 
ticipants gave particular attention to comparing 
countries with and without special vaccination 
programs, discussed strategies for the attain- 
ment of a high level of immunization, and eval- 
uated prospects for eventual eradication. They 
identified aspects of the disease and of its con- 
trol that need further research. The participants 
concluded that the challenge is to exploit the 



available vaccines and to overcome the remain- 
ing economic, logistic, and attitudinal barriers. 
Participants returned home resolved to eliminate 
measles as a universal cause of childhood misery 
and of long-term disabilities. Proceedings of the 
symposium were submitted for publication in 
Reviews of Infectious Diseases . 

International Symposium on Poliomyelitis Control 

Extensive plans were made for this project, 
which is scheduled for March [^-17, 1983, in the 
Headquarters Building of the Pan American 
Health Organization. The focus of the sympo- 
sium will be on control of poliomyelitis by means 
of immunization. Applicable to future programs 
to advance such control in both developed and 
developing countries, these recommendations 
will be based on assessment of up-to-date know- 
ledge concerning the viruses themselves, the 
current status of poliomyelitis in various parts of 
the world, and the vaccines now available. Con- 
sideration will be given to political, economic, 
and administrative aspects as they impede or 
facilitate immunization strategies and to the 
feasibility of elimination of paralytic poliomye- 
litis in the foreseeable future. Emphasis will also 
be on identification of research needs and on 
new developments and their potential contri- 
bution to improved vaccines. This project is 
being jointly sponsored by the FIC, NIAID, 
NICHD, and NINCDS of the NIH; Centers for 
Disease Control, PHS; National Center for Drugs 
and Biologies, Food and Drug Administration 
(FDA); U.S. Agency for International Develop- 
ment; Institute of Medicine, U.S. National 
Academy of Sciences; WHO; PAHO; American 
Public Health Association; Infectious Diseases 
Society of America; National Foundation for 
Infectious Diseases; The Rockefeller Foundation; 
Merieux Institute, Inc.; Smith KlineRIT; Lederle 
Laboratories; and Hoechst Aktiengesellschaft. 



International Symposium on Yaws Control 

Planning occurred during 1982 for this sympo- 
sium, which is scheduled for November or De- 
cember 1983. It will involve scientists from all 
the tropical and subtropical areas of the world 
and, in total, the discussions will cover all three 
endemic treponematoses: yaws, pinta, and en- 
demic syphilis. The main purpose of the sympo- 
sium will be to assess the current impact of yaws 
and of yaws control efforts in the world; to re- 
view current technology and strategies relevant 
to control of yaws; and to consider the feasi- 
bility of yaws eradication. Aspects of this dis- 
ease and its control that need further research 
will be identified. The proceedings of the sym- 
posium will be submitted for publication in a 
journal of broad readership, e.g.. Reviews of 
Infectious Diseases. 



12 



Internationa] Conferences and Seminars Program 



The International Conferences and Seminars 
Program fosters advanced international studies 
in the health sciences through scientific meet- 
ings and conferences that provide opportunities 
for biomedical and behavioral scientists from 
various parts of the world to share their know- 
ledge, ideas, and concerns about international 
health issues and to discuss current and future 
research endeavors and problems. 

Good scientific communications are funda- 
mental to a productive biomedical research 
program and to effective practical use of the 
results of biomedical research. Therefore, the 
FIC places a high priority on the planning and 
conduct, or funding support, of scientific sym- 
posia, conferences, and workshops. These FIC- 
supported meetings are of two types: intramural 
and grant supported. In FY 1982, the FIC pro- 
vided partial or total funding support for 8 in- 
tramural conferences and partial funding support 
for ^8 grant-supported conferences. 

Intramural conferences are arranged by 
Fogarty Scholars as well as by NIH intramural 
scientists and FIC staff. The subjects of these 
meetings are of broad scientific interest and 
draw outstanding scientists from many parts of 
the world as participants. In FY 1982, the FIC 
supported one intramural conference. Catechol 
Estrogens, organized by the Director of the NIH 
Clinical Center. The remainder were organized 
by Fogarty Scholars alone or in conjunction with 
NIH intramural scientists. These conferences are 
described in the subsequent section on the 
Scholars-in-Residence Program. 

Grant-supported conferences are initiated by 
non-NIH scientists who seek funding through 
grant applications. The NIH Division of Research 
Grants receives these applications, which are 
often given multi-Institute assignments accord- 
ing to their specific scientific nature. For those 
applications that are international in nature or 
have an international aspect, the FIC joins with 
the other assigned Institutes in the review of the 
applications and their funding, if approved. Ex- 
amples of conferences supported by the FIC in 
FY 1982 follow. 

VI International Symposium on Atherosclerosis 

The disease process that predisposes indi- 
viduals to heart attacks and stroke is athero- 
sclerosis (hardening of the arteries). Restriction 
of blood circulation due to atherosclerosis de- 
prives the heart and other organs of necessary 
oxygen and nutrients. Vital arteries are narrowed 
by mounds or plaques on the inside wall in a 
process that may take years and is associated 
with a number of risk factors. The most impor- 
tant putative risks are excessive blood choles- 
terol in the form of elevated low-density lipo- 



13 



proteins, high blood pressure, and cigarette 
smoking. 

Hardening of the arteries is the basic cause of 
coronary artery disease, the major cause of 
death in America. However, during the past 
decade there have been a 25 percent decrease in 
age-adjusted coronary heart disease and a 37 
percent decrease in age-adjusted stroke mor- 
tality. This reduction is probably attributable to 
two factors: first, lifestyle changes reducing risk 
factors and, second, improvements in care of the 
patient in the acute phase just after a myocar- 
dial infarction. 

The FIC and the NHLBI provided sponsorship 
and partial funding support for the VI Interna- 
tional Symposium on Atherosclerosis, which 
convened in West Berlin in 3uly 1982. 

The general theme of the symposium, which 
attracted more than 1,500 scientists from many 
countries, was the causes and prevention of 
atherosclerosis and its complications. The pros- 
pect for preventive cardiology seems bright. The 
decline in heart disease in America and the as- 
sociated clear evidence of changing lifestyles 
due to a decrease in the use of tobacco products, 
a reduction in the consumption of high saturated 
fat/high cholesterol foods, an awareness of the 
benefits of physical exercise, control of obesity 
and hypertension, all suggest an encouraging 
trend. However, heart disease remains a major 
problem. 

The scientific program focused on the most 
basic aspects of the disease process. The pro- 
ceedings of the symposium will be published, and 
it is expected that this volume will be a valuable 
source of information concerning progress in 
atherosclerosis research. 

Fifth International Symposium on Human 
Chlamydial Infections 

Human chlamydial infections are transmitted 
from person to person by sexual contact. Serious 
health consequences result, affecting not only 
male and female partners, but also newborn 
infants. In the United States it is estimated that 
25,000 cases of pneumonia and 50,000 eye 
infections in infants are caused yearly by 
Chlamydia . 

Chlamydial infections are the most prevalent 
of the sexually transmitted pathogens. Pelvic 
inflammatory disease is the most serious com- 
plication from chlamydial and gonorrheal in- 
fections, causing sterility and ectopic pregnan- 
cies with possible fatal consequences to mothers. 
Pelvic inflammatory disease often causes dam- 
age to the female reproductive tract, resulting 
in about 50,000 major surgical procedures each 
year in the United States. 

European scientists are at the forefront of the 
clinical and epidemiological research and control 
aspects of chlamydial infections. The FIC and 
the NIAID joined in providing partial funding 



Table 3-i.— Scholars-in-Residence, 1982 



Scholar's name and country 



Discipline and home institution 



Date of Date of 
arrival departure 



Shmuel Shaltiel, Israel 

Tomas Hokf elt, Sweden 

Klaus Kuhn 

Federal Republic of Germany 

Samuel Barondes, United States 

Franklin Bunn, United States 

David Shemin, United States 

Rolf Luft, Sweden 

Herman Kalckar, United States 

Irwin Gunsalus, United States 

Helmut Holzer, Fed. Rep. of Germany 

Howard Schachman, United States 

Theodor Wieland, Fed. Rep. of Germany 

M. Manago-Grunberg, France 

Bracha Ramot, Israel 

Hsiang-Tung Chang, China 

Gaetano Salvatore, Italy 

G. P. Talwar, India 

Sanford Palay, United States 
Mordechai Sokolovsky, Israel 
Lars Svennerholm, Sweden 

Keith Porter, United States 
Frits Orskov, Denmark 
Susan Lowey, United States 
Frank Fenner, Australia 



Biochemistry 

Weizmann Institute of Science 

Neurobiology, Karolinska Institutet 

Biochemistry 

Max Planck Institute for Biochemistry 

Psychiatry, Univ. of California, San Diego 

Hematology, Peter Bent Brigham Hospital 

Biochemistry, Northwestern University 

Endocrinology, Karolinska Institutet 

Biochemistry, Boston Univ. Grad School 

Biochemistry, University of Illinois 

Biochemistry, University of Frieberg 

Biochemistry, Univ. California, Berkeley 

Biochemistry, Max Planck Institute 

Biochemistry 

Institut de Biologie Physico-Chimique 

Hematology 

The Chaim Sheba Medical Center 

Neurophysiology, Shanghia Brain Research 
Institute, Acad. Sinica 

Endocrinology 

Istituto di Patologia Generale 

Biochemistry 

All India Institute of Medical Science 

Anatomy, Harvard Medical School 

Biochemistry, Tel Aviv University 

Neurobiology, Psychiatric Res. Center 
Gothenburg University 

Cell Biology, University of Colorado 

Microbiology, Int'l Excherichia Centre 

Biochemistry, Brandeis University 

Virology, Australian National University 



08/2^81 0^2^/82 



09/01/81 


06/15/82 


10/01/81 


09/30/82 


10/01/81 


12/31/81 


01/01/82 


03/31/82 


01/01/82 


04/01/82 


02/01/82 


04/30/82 


02/01/82 


04/30/82 


02/11/82 


04/30/82 


02/15/82 


05/15/82 


0^/01/82 


06/30/82 


04/01/82 


06/26/82 


04/01/82 


08/07/82 



04/20/82 05/30/82 



05/01/82 
06/14/82 



08/30/82 
09/24/82 



06/30/82 09/30/82 



07/01/82 
07/01/82 
08/23/82 

09/01/82 
09/10/82 
09/13/82 
09/16/82 



09/01/82 
12/22/82 
12/22/82 

12/15/82 
12/15/82 
12/13/82 
02/16/83 



14 



support for a meeting in Sweden in June 1982. 
Scientists from North America, seven European 
countries, South Africa, and Malaysia partici- 
pated. Recognizing that research on the molec- 
ular biology of Chlamydia is not well advanced 
and that a need exists for greater knowledge of 
the structure and function of this pathogen, in- 
vestigators believe that a better understanding 
could aid in improving diagnostic techniques, 
which are absolutely necessary to combat the 
infection. 

Recent advances in hybridoma technology, as 
well as in standard classical immunochemical 
methods, were reported at the symposium and 
gave a clearer picture of the surface antigens of 
Chlamydia . It is hoped that these advances will 
lead to better diagnostic methods. Genetic 
studies using recombinant DNA technology were 
presented. The meeting also covered perinatal 
infections and maternal complications, eye dis- 
eases, and preventive and control measures. 

The Third World Conference on Lung Cancer 

Smoking is associated with lung cancer and a 
host of other diseases, including cancers of the 
oral cavity, pharynx, larynx, esophagus, pan- 
creas, and bladder. Smoking is also related to 
heart and blood vessel diseases, chronic bron- 
chitis and emphysema, respiratory infections, 
and stomach ulcers. In summary, smoking is the 
single most important preventable cause of 
death and disease in our nation. 

If present trends in smoking continue in the 
United States, lung cancer will probably be not 
only the leading cause of cancer death among 
men, but also among women. 

Lung cancer is an international health prob- 
lem. The FIC and the NCI provided sponsorship 
and partial funding for the Third World Confer- 
ence on Lung Cancer held in Tokyo, Japan, in 
May 1982. Representatives of 27 nations served 
on the international program committee. The 
conference itself addressed a broad range of 
topics including prevention of lung cancer. The 
epidemiology, carcinogenesis, early diagnosis and 
staging, pathology, surgery, radiotherapy, immu- 
notherapy, cellular kinetics, and lung tumor 
markers were actively discussed. 

The conference theme was a succinct evalu- 
ation of current knowledge related to preven- 
tion, diagnosis, and treatment of lung cancer, 
focusing on both the causes of failure and the 
successful ingredients in the various program 
areas. Emphasis was placed on new approaches 
supported by ideas that evolved from the in- 
teraction among specialists from different 
countries. 

Fourth International Symposium on 
Nasopharyngeal Carcinoma 

The causes of cancer have been the focus for 
much biomedical research in the past few 



15 



decades. The varying components of lifestyle, 
e.g., nutrition, environmental factors, are being 
analyzed to identify and classify significant risk 
factors. (A risk factor increases the incidence of 
a specific disease and provides an opportunity 
for disease prevention by intervention or by 
elimination of the factor.) 

Nasopharyngeal carcinoma is a malignant 
neoplasm that has its origin at the surface epi- 
thelium of the nasopharynx. This cancer has 
attracted worldwide attention because of the 
evidence suggesting that multiple factors, in- 
cluding environmental, genetic, and viral, 
interact in the etiology of this medically inter- 
esting disease. 

The FIC and the NCI provided sponsorship and 
partial funding support for a symposium on naso- 
pharyngeal carcinoma held in Kuala Lumpur, 
Malaysia, in September 1982. Malaysia and the 
surrounding areas in Southeast Asia (Singapore, 
Hong Kong, China, and Taiwan) have a high in- 
cidence of this disease. Participants discussed 
the various facets of the disease: clinical, epi- 
demiological, virologic, immunologic, and ge- 
netic, as well as treatment and prevention. Diet, 
chemical carcinogens, and infectious agents 
were examined. A wealth of evidence from 
studies from many countries implicates the 
Epstein-Barr virus. (This virus, extremely com- 
mon in the human population, is clearly the 
cause of infectious mononucleosis.) The virus is 
thought to act in concert with other factors, 
such as immune depression and genetic factors. 



Scholars-in-Residence Program 

The purpose of the Scholars-in-Residence 
Program is to enable established scientists and 
scholars interested in international health to 
exchange information and ideas with other sci- 
entists and scholars through preparation of a 
book, monograph, or other report, as well as 
through meetings and workshops, and to col- 
laborate in research in an environment conducive 
to innovative approaches to international health 
issues. 

Scholars-in-Residence are nominated by NIH 
scientists or former Fogarty Scholars. A Scholars 
Advisory Panel of senior intramural scientists 
reviews the nominees, after which approved 
nominees are invited by the FIC as openings in 
the program become available. 

Since 1970, 100 Scholars from 21 countries 
have participated in the program. During FY 
1982, 25 Scholars participated for varying per- 
iods of time, as shown in table 3-1. The average 
stay of the Scholars was 3 months, with 21 
Scholars being in residence 6 months or less, 2 
Scholars for 8 months, and 2 Scholars for 10 or 
12 months each. 

The following two situations illustrate the way 
the Fogarty Scholars interact and share their 



extensive knowledge with NIH scientists: 

• Professor Giorgio Bernard! used the first 
two terms of his scholarship to work in the 
Laboratory of Biochemistry, NCI, where he 
collaborated with the laboratory chief. 
Professor Bernardi is one of the interna- 
tional leaders in the field of gene structure 
at the molecular level. Much of his work is 
concerned with so-called "repetitive se- 
quences" in DNA. The significance of the 
regulation and expression of DNA in health 
and disease is just beginning to be under- 
stood, but it is suspected that they are in- 
volved in modulating genetic information 
during development and tissue differenti- 
ation. Knowledge of this process may have 
implications for understanding tumor 
growth. Professor Bernardi's lifelong work 
has been concerned with the structure of 
large molecules such as proteins and nucleic 
acids. He has contributed to the methodol- 
ogy of this field that is important for much 
of contemporary molecular biology. 

The benefit to the NIH of Professor 
Bernardi's residency has been his presence 
in a major laboratory, his organization of 
the conference on "Highly Repeated DNA 
Sequences in Eukaryotes" (in collaboration 
with his host laboratory chief at the NCI, 
and attended by leading researchers in 
molecular biology and genetics), and the 
opportunity afforded him to reflect on the 
meaning of work done over many years. 

• Professor Lars Svennerholm is a world 
authority on neurochemistry. Dr. Svenner- 
holm has described many of the formal 
components of brain and nervous tissue, 
such as gangliosides and other fat soluble 
compounds of sugar and fatty acids. These 
compounds have been shown to be important 
as parts of receptors that build antigens. 
There are reports that measles virus nu- 
cleotide sequelae are found in multiple 
sclerosis plaques from patients dying of MS. 
During his stay at the NIH, Professor Sven- 
nerholm initiated collaborative investigation 
of the hypothesis that gangliosides may be 
involved in formation of human brain lesions 
since other investigators have discovered 
that gangliosides produce neurological 
symptoms in animals. A three-way collabo- 
ration began between the neurochemistry 
laboratory headed by Svennerholm in Got- 
henburg, Sweden, the VA Hospital and 
UCLA in Los Angeles, and Svennerholm's 
NIH associates. The discovery that gangli- 
osides (sugar-containing lipids) are recep- 
tors, or attachment sites, for various bac- 
terial toxins and viruses, will have applica- 
tion to the study of cancer, influenza, and 
other diarrheal diseases. 



The FIC scholarship played a key role by 
permitting Professor Svennerholm to extend 
his research through collaboration with U.S. 
scientists. This episode in Svennerholm's 
career exemplifies the kind of benefit that 
can be achieved from an extensive period of 
direct scientist-to-scientist interaction. 

Scholars-in-Residence are provided an oppor- 
tunity to organize scientific meetings and work- 
shops during their residency at the NIH. Some 
examples follow. 

• During Professor Svennerholm's residency at 
the NIH, in collaboration with colleagues 
from the NINCDS and the NIADDK, he 
organized an International Workshop on 
Gangliosides, which was held at the NIH in 
December 1981. This workshop brought 
together researchers in virology, oncology, 
biochemistry, immunology, and genetics. 

• Structure and Regulation of Connective 
Tissue Genes. This meeting was organized 
by FIC Scholar Dr. Klaus Kuhn, Max Planck 
Institute of Biochemistry, Munich, with 
scientists from the NIDR, the NHLBI, and 
the NCI. The first session considered the 
structure of genes; the second was devoted 
to human genes and genetic disorders; and 
the last dealt with regulation of collagen 
gene expression. Dr. Kuhn expects to publish 
a report on the conference in 1 983. 

• Coexistence of Neuroactive Substances in 
Neurons. The proceedings of this confer- 
ence—which was arranged by FIC Scholar 
Dr. Sanford Palay, professor of neuroanat- 
omy at Harvard, and a colleague—will be 
published in 1983 by Springer. 

Other Scholars interacted with their fellow 
scientists at the NIH in similar ways. Dr. 
Barondes, for example, spent time with members 
of the NCI Molecular Biology Laboratory, 
studying behavior of slime mold cells when they 
touch each other. For neuroscience, the study of 
how slime molds reproduce has implications for 
behavior of nerve cells, how they grow and 
organize themselves into networks during 
development. 

During 1982, there were several publications 
by Scholars who had completed their scholarships 
in previous years. One such publication, Recent 
Advances in Mucosal Immunity , Raven Press, 
1982, is the report of a meeting organized by 
Lars Hanson, one of the editors and major con- 
tributors who based his contributions to this 
effort on work performed at the NIH and in 
Sweden, analyzing results obtained in field 
studies in Pakistan on diarrheal disease in 
malnourished children. Dr. Hanson, who is pro- 
fessor of clinical immunology at Gothenburg, 



16 



continues his association with FIC activities and 
will participate in an FIC meeting on polio- 
myelitis. 

The Scholars, whose interests touch on pro- 
grams of every BID, also participate regularly in 
intramural research seminars conducted by the 
Senior Science Advisor to the Director, NIH. In 
addition, they give their own lectures and semi- 
nars. A partial list of those that took place dur- 
ing FY 1982 follows: 

• Regulation of the Cellular Response to 
Hormones: Signal Propagations and Attenu- 
ation (Dr. Shmuel Shaltiel) 

• Accretion of Gangliosides in the Brain 
During Development (Dr. Lars Svennerholm) 

• Hydrophobic Chromatography Use in the 
Resolution and Purification of Proteins and 
Cells (Dr. Shmuel Shaltiel) 

• Hydrophobic Chromatography: Proposed 
Mechanism and Its Relevance to Biorecog- 
nition (Dr. Shmuel Shaltiel) 

Other conferences organized through collabor- 
ation between FIC Scholars and NIH intramural 
scientists were: 

• Workshop on Hemoglobin Assembly and 
Catabolism. Organized by Professor 
Franklin Bunn, of Harvard University (while 
a Fogarty Scholar-in-Residence), in con- 
junction with an intramural scientist from 
the NIADDK, this workshop investigated the 
problems of hemoglobin and hemoglobin- 
related inherited blood diseases. These 
diseases include thalassemia (in which too 
little hemoglobin is produced), which results 
in anemia. Abnormal hemoglobins (the 
oxygen-carrying portion of the red blood 
cell) are a serious health problem through- 
out the world; recently developed technol- 
ogy for growing erythroid cells and other 
new tools of molecular biology provide new 
research opportunities for understanding the 
normal and the diseased states. 

• International Workshop on the Influence of 
the Environment on Leukemia and Lym- 
phoma Subtypes. Organized by FIC Scholar 
Dr. Bracha Ramot, professor of medicine at 
Tel Aviv University, this meeting brought 
together experts from around the world to 
discuss the epidemiology of lymphoid neo- 
plasia in the light of modern immunological 
concepts of these diseases. 

• Translational/Transcriptional Regulation of 
Gene Expression. This conference was 
organized by FIC Scholar-in-Residence Dr. 
Marianne Grunberg-Manago, professor of 



biology at the Institute of Biology in Paris. 
She and a colleague at the NHLBI, Dr. Brian 
Safer, edited the proceedings, which were 
published by Elsevier in September 1982. 

• Endogenous Lectins May Play Many Roles 
(Dr. Samuel Barondes) 

• The Structure of CoUagens and Errors in 
Their Macromolecular Organization in Some 
Connective Tissue Diseases (Dr. Klaus Kuhn) 

• Metabolic Interconversion of Fructose 
Biphorphatase in Yeast (Dr. Helmut Kolzer) 

• An Approach to Diabetes Health Care in 
Sweden (Dr. Rolf Luft) 

• Immunological Approaches to the Control of 
Fertility (Dr. G.P. Talwar) 

• Muscarinic Receptors in the Endocrine 
System (Dr. Mordechai Sokolovsky) 

Fogarty Scholars-in-Residence and NIH 
intramural scientists also collaborate in the 
arrangement and presentation of seminars. Of 
the 12 seminars that took place in FY 1982, the 
following are illustrative: "Mechanisms for Syn- 
thesis and Inactivation of Peptides," "Molecular 
Mechanisms of Brain Receptors," "The Coopera- 
tive Oxygenation of Hemoglobin," "Red Cells 
Are Not Created Equal: The Consequences for 
Sickle Cell Anemia and Malaria," "Chemical 
Mechanisms of Action of Insulin," and "Dual 
Information Coding in Retinal Ganglion Cells: 
Small Eye Movements and Visual Acuity." 



Foreign Scientists Assistance 



The Foreign Scientists Assistance Programs of 
the FIC provide coordination, guidance, and 
facilitative services to the NIH BID's in the 
administrative management of the NIH Visiting 
Program and the NIH Guest Researchers Pro- 
gram. These programs offer the opportunity for 
talented scientists throughout the world to en- 
gage in collaborative research with NIH sci- 
entists. Through these programs, the NIH is able 
to take advantage of the research services of 
over 1,400 scientists from about 60 countries. 
The FIC staff also supports visiting programs of 
the National Center for Drugs and Biologies 
(NCDB) of the FDA, and the National Institute 
of Mental Health (NIMH) and the National 
Institute on Alcohol Abuse and Alcoholism 
(NIAAA) of the Alcohol, Drug Abuse, and Mental 
Health Administration (ADAMHA). 

Under the NIH Visiting Program, foreign 
researchers are invited to NIH laboratories by a 



17 



senior investigator and usually stay from 1 to 3 
years. The relationship between the NIH scien- 
tific community and its foreign colleagues is 
based on mutual benefits; the Visiting Program is 
both a learning and a sharing process whereby 
benefits accrue to each side. Foreign scientists 
join NIH laboratories for a limited time to meet 
programmatic needs and are provided the op- 
portunity to explore promising leads—with lim- 
ited investment from the NIH. The foreign sci- 
entists enjoy enhanced capability from exposure 
to modern research methods for effective re- 
search in their chosen fields upon return to their 
home institutions. 

The NIH Visiting Program has three levels: 
Visiting Fellow, Visiting Associate, and Visiting 
Scientist. The Visiting Fellows, those whose 
postdoctoral experience in medicine or health 
science does not exceed 3 years, receive awards 
for advanced research experience. Their scien- 
tific potential comes to the attention of NIH 
senior investigators through their presentations 
at meetings, workshops, etc., and through their 
contributions to scientific literature. The mid- 
level Visiting Associates have between 3 and 6 
years of postdoctoral experience and the neces- 
sary knowledge to further a particular study. At 
the top level are the Visiting Scientists with 
more than 6 years of postdoctoral experience 
and exceptional abilities that enable them to 
make a significant contribution to the ongoing 
research of the sponsoring BID. Like Visiting 
Associates, Visiting Scientists are appointed for 
the performance of services for the NIH. In all 
instances awards and appointments are made on 
an invitational basis only. 

The total NIH Visiting Program participation 
for all BID'S (including NIMH and NIAAA of 
ADAMHA and FDA's NCDB) served by the For- 
eign Scientists Assistance Programs in FY 1982 
was 1,523 individuals, including 1,093 foreign 
scientists from 56 countries. There were 7^9 
Visiting Fellows, 192 Visiting Associates, and 152 
Visiting Scientists at a cost of $17.2 million of 
intramural research funds, an increase of 268 
individuals over the FY 1981 total of 1,255 and 
an increase in total funding of $IA million. 

In addition to administering the NIH Visiting 
Program, the Foreign Scientists /assistance Pro- 
grams provide advisory services in varying de- 
grees, particularly in immigration matters, to 
other foreign scientists at the NIH. In FY 1982 
the Foreign Scientists Assistance Programs 
assisted 430 other foreign scientists of whom 77 
percent were Guest Researchers, who are usually 
funded from sources within their home countries; 
10 percent were appointed as special experts 
funded by the BID's; and 13 percent represented 
scientists on bilateral agreements, FIC Inter- 
national Research Fellows located at the NIH, 
and Fogarty Scholars. 

Most of these foreign scientists were from 
Europe and Asia, with a number from the Latin 



and other North American countries, and the 
African and Middle Eastern countries. 

Illustrative descriptions of projects in which 
Visiting Scientists and Foreign Guest Research- 
ers have been involved are provided throughout 
this report, in the sections that describe each of 
the BID programs. 



International Research and Awards 

Several types of international fellowship pro- 
grams are supported fully or partially by the FIC 
and are administered by the FIC. These programs 
facilitate the exchange of research experiences 
and information by enabling foreign scientists to 
pursue their research interests in U.S. labora- 
tories or, conversely, by providing opportunities 
for U.S. researchers to work in foreign labora- 
tories. These programs are: 

• International Research Fellowships, 

• WHO/NINCDS/FIC International Neuro- 
sciences Fellowships, 

• WHO/NIAID International Tropical Diseases 
Fellowships, and 

• Senior International Fellowships. 

Listed below are four other fellowship pro- 
grams for U.S. scientists to study abroad, ad- 
ministered by the FIC but supported by the Gov- 
ernments of France, the Federal Republic of 
Germany, Sweden, and Switzerland: 

• French National Institute of Health 
(INSERM) Fellowships, 

• Alexander von Humboldt Foundation Fel- 
lowships, 

• Swedish Medical Research Council Fellow- 
ships, and 

• Swiss National Science Foundation Fellow- 
ships. 

Under individual cooperative agreements, the 
FIC administers health scientist exchange pro- 
grams with five countries: France (CNRS), 
Poland, Romania, the U.S.S.R., and Yugoslavia. 
NIH participation in the Special Foreign Cur- 
rency (P.L. ^&0) Program is administered by the 
International Research and Awards Programs. 
Each of these programs is discussed in detail in 
the following section. 

International Research Fellowships 

The International Research Fellowship (IRF) 
Program provides opportunities for postdoctoral 



IS 



biomedical or behavioral scientists in the form- 
ative stages of their research careers to extend 
their research experiences in a laboratory in the 
United States. These fellowships forge rela- 
tionships between distinguished U.S. scientists 
and qualified scientists in other countries to 
resolve health-related problems of mutual 
interest. 

During FY 1982, there were ^7 participating 
countries with Nominating Committees. Thirty- 
four Nominating Committees recommended 127 
applicants for the program. Subsequent to sci- 
entific peer review conducted by the NIH, 9^ (78 
percent) were funded. Recipient countries of 
fellowship awards are shown in table 3-2. 



Table 3-2.— International research fellowship 
awards by country /area of applicants, 1 982 



Americas 


18 


Europe 


50 


Argentina 


5 


Austria 


1 


Brazil 


5 


Belgium 


3 


Chile 


k 


Denmark 


3 


Mexico 


2 


Finland 


5 


Peru 


1 


France 


5 


Uruguay 


1 


Ireland 


k 






Italy 


5 






Netherlands 


2 


Africa 


3 


Norway 


2 


Nigeria 


2 


Poland 


H 


Sudan 


1 


Spain 


6 






Sweden 


6 


Asia and Far East 


18 


Switzerland 


1 


Australia 


4 


United Kingdom 


2 


India 


3 


Yugoslavia 


1 


Japan 


5 






Korea 


1 


Middle East 


5 


New Zealand 


3 


Israel 


k 


Taiwan 


2 


Lebanon 


1 



In FY 1982, a Nominating Committee was 
formed in China, and the Nominating Committee 
in the West Indies was reactivated. Applications 
are expected from these committees in Septem- 
ber 1983. 

Examples of collaborative research activities 
undertaken by IRF awardees are described in the 
following section. 

• Renal involvement in systematic lupus 
erythematosus (SLE) is characterized by 
many different clinical and morphological 
features. To evaluate the effects of treat- 
ment and the prognosis on different types of 
SLE, an IRF awardee working with a sci- 
entist from Columbia University determined 
the frequency and amount of immune com- 
plex deposits in the tubular basement mem- 
brane and in the interstitium from autopsy 
cases of renal nephritis. These findings were 



correlated with (1) the degree and type of 
interstitial inflammation, interstitial edema 
and fibrosis and tubular atrophy; (2) the 
type, severity, and activity of glomerular 
lesions; (3) the degree of renal functional 
impairment; and (4) the long-term prog- 
nosis. The results indicate that, in renal 
biopsies from patients with lupus nephritis, 
tubular basement membrane and intersti- 
tium deposits are usually associated with 
more severe and active glomerular disease. 
Renal insufficiency is more common and 
more pronounced in these patients, and the 
long-term prognosis is considerably worse. 
Renal function was reasonably good in 65 
percent of the cases in patients with tubular 
basement membrane deposits ^ years after 
the original biopsy in contrast to about 85 
percent for patients without these deposits. 
These findings are of potential significance 
for selection of the most appropriate ther- 
apy in these patients. 

• Subjecting premature babies to oxygeri- 
enriched breathing mixtures can result in 
retrolental fibroplasia or retinopathy of 
prematurity. The high-oxygen concentration 
inhibits normal development of the retinal 
vessels by constricting them, which leads to 
vasoproliferation. Using the cat as an ani- 
mal model for retinopathy, one IRF awardee 
working with a scientist from Duke Uni- 
versity was able to determine the contri- 
butions of oxygen levels in the choroid and 
the iris under different physiologic and 
pathologic conditions. This information with 
further experimentation can be used to 
understand the various factors or changes 
that take place to produce dilation or con- 
striction of blood vessels, the changes that 
cause retinopathy of prematurity. 

• Diabetes mellitus, which is the fifth leading 
cause of death in the United States, has 
been diagnosed in over 5 million Americans 
and probably affects an additional 5 million 
people. Several lines of evidence suggest an 
involvement of the immune system in the 
etiology of insulin-dependent diabetes mel- 
litus. One IRF awardee in collaboration with 
an NIH intramural scientist studied the 
capacity of islet cell surface antibodies to 
lyse human beta cells as well as other islet 
cells. The Fellow demonstrated that islet 
cell surface antibodies react with different 
antigens on the pancreatic islet cells and 
that therefore these antibodies are hetero- 
geneous in nature. Some of the islet cell 
antibodies and the islet cell surface anti- 
bodies are cytotoxic for islet cells; thus, 
these antibodies may play a role in the 
pathogenesis of insulin-dependent diabetes 
mellitus. This research also demonstrated 



19 



that islet cell IgM antibodies can often be 
detected in the area of prediabetic first- 
degree relatives of patients with insulin- 
dependent diabetes mellitus and gestational 
diabetes (30 percent and ^6 percent, re- 
spectively). 



International Neurosciences Fellowships 

The International Neurosciences Fellowship 
Program was established in 1977 in cooperation 
with the NINCDS and WHO and is administered 
by the FIC with funds provided by NINCDS. 
Three awards were made in FY 1982 to scientists 
in China. 



International Tropical Diseases Research Fellowships 



Table 3-3.~Senior International Fellowship 
awards by country of destination 



Americas 


2 


Europe 25 


Canada 


1* 


France 2* 


Chile 


1 


Federal Republic 
of Germany 1 


Asia and Far East 


1 


Italy ^* 


Australia 


1 


Sweden 2 
Switzerland li 


Middle East 


3 


United Kingdom 12 


Israel 


3* 





*Two scientists have collaborative research 
projects in two countries. 



The FIC in cooperation with the National 
Institute of Allergy and Infectious Diseases and 
with the United Nations Development Program 
(UNDP)/World Bank/WHO Special Program for 
Research and Training in Tropical Diseases has 
established a limited number of postdoctoral 
fellowships in tropical diseases. Candidates for 
these fellowships are from countries in which the 
following diseases are endemic: malaria, schis- 
tosomiasis, leishmaniasis, trypanosomiasis, fil- 
ariasis, and leprosy. Two awards jointly funded 
by the FIC and the NIAID in FY 1982 and were 
made to scientists from China and Egypt. 



Senior International Fellowships 

The Senior International Fellowship (SIF) Pro- 
gram provides opportunities for established 
biomedical or behavioral researchers to do col- 
laborative research in a foreign institution. SIF's 
enhance the exchange of ideas and information 
about the latest advances in specific areas of 
medicine, both basic and clinical. They also lead 
to improvement in the research, education, and 
clinical potential of U.S. nominating institutions, 
which profit from the scientists' experiences 
abroad. During FY 1982, U.S. institutions nomi- 
nated 71 scientists for SIF's. Of this number, 29 
(^1 percent) were funded. Table 3-3 lists the host 
countries that received SIF awardees. 

Examples of collaborative research projects 
undertaken by SIF awardees include: 

• Widespread in the population, herpesvirus 
infections are responsible for oral and gen- 
ital infections and for such infections as 
chickenpox and shingles. This virus is not 
now controlled by vaccinations. Develop- 
ment of suitable herpesvirus vaccines will 
require the identification and production of 
the protective antigens. An SIF awardee in 



20 



collaboration with a scientist from the 
Institute of Medical Microbiology in the 
Federal Republic of Germany studied the 
frequency of cytotoxic T lymphocyte pre- 
cursors in lymphoid population from normal 
mice and from mice infected with live her- 
pesvirus or vaccinated with inactivated 
herpesvirus. The Fellow was able to show 
that only mice exposed to live herpesvirus 
developed large numbers of cytotoxic T 
lymphocyte precusors and that inactivated 
virus vaccine was a poor stimulation of such 
cells. 

Since the cytotoxic T lymphocyte re- 
sponse is considered important in immunity, 
these results would indicate that if inacti- 
vated herpesvirus is to be used as a vaccine, 
a suitable and safe adjuvant that can stim- 
ulate adequate cytotoxic T lymphocyte 
responses may be identified. 



• Researchers have shown that in the rat 
model of streptozotocin-induced diabetes 
mellitus, the disease can be treated by 
transplantation of fetal pancreas. The major 
obstacle remaining before general appli- 
cation of this method is the problem of 
rejection. An SIF awardee and a scientist 
from the Walter and Eliza Hall Institute in 
Australia explored methods to prevent re- 
jection of transplanted fetal pancreas al- 
lographs using the rat and pig as animal 
models. Several methods proved partially 
effective in diminishing rejection of ailo- 
graphed pancreas: (1) prolonged culture (3 
weeks) of fetal tissue in 95 percent oxygen; 
(2) collagenase digestion of pancreas fol- 
lowed by short-term (k days) culture of 
tissue; (3) oral administration of cyclosporin 
A; and (^) ultraviolet treatment of donor 
spleen cells. 



• Detection of small amounts of biomolecules 
is a challenge to scientists who are studying 
molecules present in small amounts in var- 
ious organs or body fluids. One SIF awardee, 
in collaboration with a scientist from the 
Imperial College of Science and Technology 
in England, attempted to develop a new 
methodology for sequence analysis of nano- 
mole or less amounts of specific proteins. In 
one project, using a newly developed ioni- 
zation technique of fast atom bombardment 
and a high field magnet sector mass spec- 
trometer, the awardee was able to show 
that in the dephosphorylation of casein (a 
milk protein), the dephosphorylation pro- 
ceeds with high specificity and sequentially 
removes up to five phosphate groups from 
serine residues. This methodology can be 
used to elucidate biochemical structures 
such as the various neuropeptides. 

Special Emphasis Senior International 
Fellowship Programs 

These programs have the same purpose and 
eligibility criteria as the SIF Program. Since 
these programs are administered by the FIC in 
cooperation with the NIADDK and the NINCDS, 
the emphasis is on arthritis, diabetes, and epi- 
lepsy. During 1982, no awards were made in 
these programs. 

Foreign Government Fellowships 

Currently four countries provide fellowships 
for U.S. scientists to conduct research abroad: 
France, the Federal Republic of Germany, Swe- 
den, and Switzerland. These are sponsored, re- 
spectively, by INSERM, the Alexander von Hum- 
boldt Foundation, the Swedish Medical Research 
Council, and the National Science Foundation of 
Switzerland, The FIC publicizes these programs 
and advises prospective applicants about the 
programs. With the exception of the Alexander 
von Humboldt Fellowship applications, the NIH 
reviews the applications for scientific merit and, 
afterwards, the FIC forwards the applications 
and summary statements to the appropriate 
awarding agency to make the funding decisions, 
whereas the Alexander von Humboldt Foundation 
reviews all its own applications. In FY 1982 
three applications were funded under the Swe- 
dish program and five under the Swiss. 

Individual Health Scientist Exchange Programs 

The FIC, on behalf of the Public Health Ser- 
vice, administers Individual Health Scientist 
Exchange Programs with France, Hungary, Po- 
land, Romania, the U.S.S.R., and Yugoslavia. The 



exchange programs, whose basic goal is to ex- 
pand and disseminate scientific knowledge, fos- 
ter new research ideas through the promotion of 
scientist-to-scientist contacts. As components of 
broader intergovernmental bilateral agree- 
ments for cooperation in science and technology, 
including health, these programs serve the broad 
range of health interests of the PHS and the 
respective foreign ministries of health. They 
provide opportunities for health professionals to 
become familiar with various aspects of public 
health and biomedical research activities of the 
participating host country. By providing support 
for short- and long-term exchanges, the pro- 
grams encourage and facilitate direct collabo- 
ration and communication between health and 
biomedical communities of the United States and 
the participating countries. 

Under an agreement between the NIH and the 
CNRS, the two institutions support the work of 
U.S. scientists in French laboratories and the 
work of French scientists in U.S. laboratories for 
periods of 6 to 12 months. The type of activity 
undertaken with a host laboratory may include 
the conduct of basic or clinical research, famil- 
iarization with or utilization of special tech- 
niques and equipment not otherwise available, 
and/or related cooperative efforts. Each side 
supports 75 person-months of work annually. 
During FY 1982, 9 U.S. scientists worked in 
French laboratories, and 1 1 French scientists 
worked in U.S. laboratories. 

Under an overall science and technology 
agreement with Hungary, a Program of Cooper- 
ation and Exchanges that was initiated in FY 
1982 now provides for individual health scientist 
exchanges up to 12 months from each country. 

• Under these programs, during FY 1982, 
three Polish scientists visited the United 
States for familiarization with vascular and 
abdominal surgery, surgical treatment of 
tracheal strictures, and micro and laser 
surgery in ophthalmology. 

• Four Romanian scientists spent varying 
periods of time at U.S. universities with 
research interests in the following areas: 
electron microscopy, cancer, recent ad- 
vances in understanding pain, and surgery of 
the spine. 

• A six-member team of American neuro- 
surgeons visited the Soviet Union to study 
research in new computerized CT scanning 
procedures and stereotactic computerized 
methods for treatment and removal of cen- 
tral nervous system lesions. During this 
visit, the delegation discussed and ex- 
changed information on problems inherent in 
this method and on the neurobehavioral 
effects on behavior before and after ster- 
eotactic removal. 



21 



• One American scientist visited Moscow and 
Leningrad to study clinical and research 
work in otolaryngology. Several Soviet sci- 
entists interested in such diverse topics as 
immunology, interferon research, eye sur- 
gery, neurosurgery, and artificial organs 
visited the United States in FY 1982. 

• Activities under the U.S.-Soviet Health 
Exchange Program were suspended mid-year 
in order to evaluate the program. The FIC is 
attempting to identify areas of excellence 
in Soviet science to encourage greater U.S. 
participation. Activities are expected to 
resume in FY 1983. 

• Four Yugoslav health scientists visited the 
United States to study various phases of 
hospital administration and nursing. 

Table 3-^ provides summary data on these 
exchange programs. 



Special Foreign Currency Program 

Using unique financial resources, the Special 
Foreign Currency (P.L. 'fSO) Program supports 
biomedical research, translation, and dissemi- 
nation of information in the health sciences in 
selected countries. In India and Pakistan, U.S.- 



owned "excess foreign currencies" are used. In 
Poland and Yugoslavia, U.S.-owned "near excess 
foreign currencies" appropriated to the Depart- 
ment of State are deposited in joint funds where 
they are matched by the foreign country. In 
Egypt, negotiation of an analogous source of 
funds is underway but not completed. Admini- 
stered by joint boards, these funds are allocated 
to the NIH and to other agencies to support 
biomedical research of mutual interest to the 
United States and Poland or Yugoslavia. 

These foreign currencies cannot be exchanged 
for U.S. dollars or other convertible currencies, 
nor can funds be used without the consent of the 
foreign government. Central National Coordi- 
nating Committees, in addition to joint boards on 
which the United States is represented, review 
technical merit and ascertain concurrence with 
national policies, procedures, and priorities on 
health and scientific issues and take into account 
political, economic, and other factors. 

The program is collaborative in character. 
Research proposals must represent a joint effort 
of U.S. and foreign scientists within their areas 
of professional interest and competence and in 
conformity with national priorities. The program 
comprises projects covering a wide spectrum of 
biomedical and health sciences. Attempts are 
made to draw upon resources unique to the host 
country, such as cultural, ethnic, anthropolog- 
ical, ecological, and disease patterns. Promising 



Table 3-(f.— Rate of exchange of U.S. and foreign scientists since 
initiation of international research and awards programs 









Average 




FY 1982 




Total U.S. 






U.S. 


Other 




Total country 






Maximum 


length of 


scientists 


scientists 


scientists 


scientists 




Date 


(man-mo 


stay 


to country 


to U.S. 




to country 


to U.S. 


Country 


initiated 


per year) 


(man-mo) 


no. m-m 


1 no. 


m-m 


(man-mo) 


(man-mo) 


France 


1979 


75 


9.5 


10 53 


10 


55 


132 


18^.5 


(CNRS) 


















Hungary 


1982 


12 




none 


none 








Poland 


1979 


30 


3.5 


none 


^ 


5.5 


21 


60.5 


Romania 


1967 


2^ 


lA 


none 


3 


6.5 


30.5 


96 


U.S.S.R. 


1961 


20* 


2.0 


7 3 


7 


8 


309 


536.5 


Yugoslavia 


1 979 unspecified 


2.3 


none 


^ 


3.5 


11 


9 



*The FIC instituted a moratorium on this exchange program during FY 1982. As of January 1983, the 
program has been resumed with a maximum of 5 man-months per country. 



22 



projects concerned with investigation of the 
more fundamental aspects of biomedical prob- 
lems as well as clinical and behavioral science 
investigations and epidemiological studies are 
represented in the program. 

India 

In India, the Working Group on Medical and 
Health Sciences of the Joint Commission on 
Economic, Commercial, Scientific, Technologi- 
cal, Educational and Cultural Cooperation, 
established by a bilateral agreement signed 
October 28, 197^, has shaped and guided the 
collaboration with the NIH in recent years. The 
Fifth Meeting of the Subcommission in 1980 was 
notable for its shift from the repeated emphasis 
of previous meetings upon indigenous infectious 
and parasitic diseases of primary interest to the 
Indian Council of Medical Research and Ministry 
of Health (tuberculosis, leprosy, streptococcal 
infections, diarrheal agents, hepatitis, enceph- 
alitis, malaria, filariasis, leishmaniasis) to the 
inclusion of interests in molecular and cellular 
biology. With the intervention of the Department 
of Science and Technology in the Sixth Meeting 
of the Subcommission in December 1981, the 
trend toward modern biological sciences was 
reflected by changing the name to the Working 
Group on Life Sciences, Medical and Health 
Sciences and by designating a subgroup on medi- 
cal and health sciences and a subgroup on life 
sciences. The latter was to stimulate research in 
modern biology, genetic engineering, interferon, 
chemo-receptor physiology, and macromolecular 
dynamics. 

Pakistan 

At present no projects are active in Pakistan. 
The past program has been modest in size as 
judged by the number of projects. There is 
neither a science and technology nor a health 
agreement between the United States or its 
agencies in Pakistan. The Director General of 
the Pakistan Medical Research Council visited 
the NIH in FY 1982. During the discussions, such 
areas of mutual interests were identified as 
cancer, infectious disease, immunology, and 
training, which can serve as the basis for col- 
laboration as clinical centers under construction 
in Pakistan are completed. 

Poland 

The Polish program, initiated by the U.S.- 
Polish 3oint Committee for Cooperation in the 
Field of Health, was established in 1962 and for 
several years has had as its areas of primary 
interests and priorities cancer, cardiovascular 
disease, occupational health, maternal and child 
heeilth, rehabilitation, neurosciences, metabolic 
and endocrine disturbances, organ transplanta- 



tion and nephrology, and health protection or- 
ganization. The collaborative program experi- 
enced a major disruption in FY 1982 for the first 
time since its inception as a result of the ter- 
mination of the Science and Technology Agree- 
ment and the sanctions imposed upon Poland. 

With the establishment in recent years of the 
U.S. -Polish Joint Board on Scientific and Tech- 
nological Cooperation and its Marie Sklodowska 
Joint Fund, the U.S. -Polish Joint Committee for 
Cooperation in the Field of Health, although 
established earlier under a separate agreement, 
became a virtual subsidiary as the result of the 
joint fund's support of health projects. The 
agreement that established and maintained the 
joint board and its joint fund was scheduled for 
renewal before its expiration date of December 
31, 1981. To replenish the resources of the joint 
fund, the Department of State was planning to 
provide $2 million in zlotys annually from its 
appropriation beginning in FY 1982 for a subse- 
quent 5-year period to be matched equally by the 
Polish Government. Prevailing economic condi- 
tions were such that the Polish side found it 
necessary to negotiate for a portion of the de- 
posits to be made in dollars for basic scientific 
supplies. During the resulting delay in negotia- 
tions, martial law intervened. Then sanctions 
were imposed as the result of the expulsion of 
the U.S. Science Attache, and the agreement 
authorizing the joint board lapsed. Although 
there are uncommitted funds apportioned for 
biomedical and health sciences in the joint fund, 
their availability remains indeterminate. 

Yugoslavia 

The present Yugoslavia program is under the 
auspices of the U.S.-Yugoslavia Joint Board on 
Scientific and Technological Cooperation, which 
includes the health sciences. In contrast to other 
joint boards, no list of priority areas has been 
developed for the collaborative program in 
Yugoslavia. A delegation of Yugoslav scientists 
visited the United States at the time the joint 
board was established to identify productive 
areas for collaboration. The topics suggested 
were medicine, biology, cardiovascular disease 
(especially hypertension), malignancy (including 
etiology, pathology, therapy, and immunology), 
neurosciences, hemoglobinopathy, immunology, 
drug toxicity, and occupational diseases. The 
program, as it has developed, includes many of 
these topics. In addition, the Republics ordinarily 
propose projects in keeping with their individual 
local priorities and emphasize economic devel- 
opment and short-term applicability. 

The Yugoslav side usually submits a list of 
15-25 health science proposals, received from 
the science organizations in the several Repub- 
lics of Yugoslavia. The U.S. researchers and 
institutions also submit proposals. The joint 
board meets twice a year at which time it re- 



23 



views these proposals and selects projects to be 
funded. The joint fund is replenished annually by 
equal matching deposits of dinars, in the total 
amount of $3.^^ million, with the U.S. deposit 
made by the Department of State from its ap- 
propriation. The DHHS is allotted 11 percent of 
this money, which is used to fund the selected 
projects from the various PHS agencies. 

Egypt 

In Egypt the U.S.-Egypt Joint Working Group 
on Health Cooperation and its Subcommittee for 
Biomedical Research, Infectious and Parasitic 
Diseases has had a major role in shaping the 
U.S.-Egyptian collaboration. Under its direction 
the NIH program underwent a transition from 
investigator-conceived projects representing 
academically oriented research interests to 
mission-oriented projects directed at national 
health goals: namely, raising citizens' health 
awareness; reducing infant, child, and maternal 
mortality rates; and reducing birth rates. Popu- 
lation groups for special attention are infants, 
children of school age and under, mothers, 
workers, the aged, low income, and medically 
underserved. In addition to undergoing a review 
to determine the potential for immediate con- 
tributions to the objectives and populations, 
projects are also evaluated for their contribution 
to such collateral aspects of importance as 
institution building, manpower training, and 
interrelationships with other projects. 

The last meeting of the 3oint Working Group 
and its committees was held in June 1981. The 
remaining excess currency funds available to the 
NIH were committed at the end of FY 1981. The 
proposed Multisector Science and Technology 
Project expected to provide funds for FY 1982 
and the subsequent 3 years was not approved. 
This project was to be supported by the USAID 
with matching funds from the Government of 
Egypt and funds from Title III of P.L. i+SO, which 
formerly funded the Special Foreign Currency 
Program under the authorization of Title I. 
Authorization for use of funds from this latter 
source has not been provided. At a planning 
meeting of representatives of the Joint Working 
Group in August 1982 in Cairo, concern was 
expressed about the lack of action on the Multi- 
sector Science and Technology Project. During 
the subsequent visit to the United States by the 
Minister of Health of Egypt, the status of the 
existing collaboration was reviewed and plans 
were made for a meeting of the Joint Working 
Group on Health Cooperation to be held in 1983. 

Scientific Accomplishments 

The program in Egypt has, however, achieved 
some noteworthy scientific gains. For example, 
it fostered the development of the eye disease 
and blindness research center at the University 



of Alexandria in collaboration with the Proctor 
Foundation for research in ophthalmology of the 
University of California. This center evolved 
from a blindness registry and epidemiological 
studies that have shown that t^.7 percent of the 
rural population and 1.5 percent of the urban 
population in Northern Egypt have significant 
visual disability. At least half of the loss of 
vision in rural areas and one-third in urban areas 
is due to prevalent ophthalmias and infectious 
diseases that are treatable and preventable. This 
study has also established the role of Chlamydia , 
the causative agent of trachoma, in bronchitis, 
pneumonias and diarrheal diseases, which ac- 
count for an excessive mortality among Egyptian 
children. 

A molecular biology study at the Indian In- 
stitute of Science in Bangalore, India, has pro- 
duced a number of theoretical conformations of 
DNA, among them a "left-handed molecule," 
which was in contradiction to contemporary 
thought but in subsequent experimental studies 
by scientists in the United States was found to 
occur naturally. Such information is a key to the 
understanding of biological processes and has 
application to prevention and treatment of ge- 
netic diseases. 

The National Library of Medicine's Critical 
Review Program for writing and publishing re- 
views of health science topics in Poland has 
produced a number of widely accepted publica- 
tions. A review of "Human Neutrophils" brought 
together the findings and concepts of the bril- 
liant hematologic school in Krakow and of other 
Polish hematology schools. A summary of the 
biology of the human neutrophilic granulocyte, a 
white blood cell, is given with emphasis upon the 
clinical significance, especially of the non- 
specific resistance of people to various microbial 
agents and the recent research evidence of the 
role of neutrophiles in antitumor immunity. 
Another Polish review, "Industrial Noise Pollu- 
tion and Hearing Impairment," is a product of 
this program and is intended for audiologists, 
otolaryngologists, industrial health officers, and 
others such as physiatrists who need a funda- 
mental understanding of noise and hearing 
problems from health, social, and economic 
points of view. The topics included will be of 
great interest to those involved in rehabilitation 
medicine. 



International Coordination and Liaison 

International coordination and liaison (ICL) 
activities conducted by the FIC provide for 
coordination of NIH international relationships 
to facilitate the interaction of scientists, to 
assist in the exchange of scientific information, 
and to enhance communications between the NIH 
and other international offices or agencies. 
These activities provide policy guidance, coor- 



2^ 



dination, and general oversight for the partici- 
pation of the NIH with other U.S. agencies in 
bilateral cooperative agreements between the 
U.S. Government and other countries. 



BUateral Agreements 

The United States is contributing significantly 
toward the resolution of a broad spectrum of 
international health problems through its do- 
mestic research and related efforts, its cooper- 
ative health relationships with other countries, 
and its participation in the programs and activ- 
ities of international organizations, notably WHO 
and PAHO. Formal intergovernmental agree- 
ments may take a variety of forms, ranging from 
those of broad scope for educational, cultural, 
and scientific exchange to more specific ones in 
science and technology or the health fields. In 
some instances, a health agreement may be 
subsidiary to a broader agreement in science and 
technology. Less formal technical level agree- 
ments may also exist directly between counter- 
part institutes for a specific purpose. As a basis 
for cooperation in particular situations and cir- 
cumstances, formal agreements often use special 
resources or form a basis for surmounting con- 
straints of different social and political systems. 

Coordination of NIH participation in all bi- 
lateral agreements that involve NIH components 
and scientists is a continuing responsibility of 
the FIC. The Assistant Secretary for Health has 
now designated the NIH as the lead admini- 
strative agency for bilateral programs with 
Belgium, France, the Federal Republic of Ger- 
many, Hungary, 3apan, Poland, Romania, Vene- 
zuela, and Yugoslavia. Accordingly, ICL staff 
carry out this role for the NIH. 

During the last decade, international health 
research and related activities conducted by 
DHHS/PHS, and particularly by the NIH, have 
increasingly been planned collaborative efforts 
and have been instituted through special bilat- 
eral arrangements. Since the first formal pro- 
gram was signed with 3apan in 1965, more than 
20 bilateral health agreements have been signed 
directly between DHHS officials and officials of 
foreign ministries of health. 

At present there are ^2 agreements that in- 
volve the NIH with 26 countries, among which 
are China, Egypt, the Federal Republic of Ger- 
many, India, Israel, Japan, Nigeria, the U.S.S.R., 
and various countries of Eastern Europe. The 
NIH participates with the following countries in 
broad agreements covering science and tech- 
nology cooperation for which the Department of 
State or the National Science Foundation serves 
as the executive agency: Egypt, France, India, 
Israel, Italy, 3apan, Nigeria, Pakistan, Poland, 
Romania, Spain, Venezuela, and Yugoslavia. The 
NIH occasionally participates in agreements with 
Argentina, Australia, Brazil, Greece, Kenya, 



Mexico, Senegal, and Zimbabwe. Although the 
FIC has a role in the administration of bilateral 
agreements, the scientific content of the proj- 
ects supported in foreign countries is selected by 
the collaborating scientists at the NIH in coop- 
eration with the foreign scientists. 

Significant events that occurred during FY 
1982 included: 

• The U.S.-P.R.C. Joint Science and Tech- 
nology Commission Meeting, which was held 
in Washington on October 15-17, 1981. The 
Joint Commission governs the agreement 
under which the Health Protocol operates. 
The Health Protocol continues to be very 
active with exchanges of U.S. and Chinese 
scientists in the areas of cancer (NCI), 
infectious diseases (NIAID), and cardio- 
vascular epidemiology (NHLBI). 

• The U.S.-Federal Republic of Germany 
agreement for cooperation in biomedical 
research technology, which was renewed in 
September 1982 for a second 5-year term 
with some small amendments. A workshop in 
the cardiovascular area held in Bethesda in 
October 1981 concerned cooperative ac- 
tivities related to the German National 
Health Survey. In July 1982, the FRG Min- 
ister of Youth, Family and Health visited 
the NIH. 

• A Memorandum of Understanding between 
the Ministry of Social Affairs and Health, 
Finland, and DHHS, which has been nego- 
tiated and is expected to be signed in FY 
1983. The Secretary General of the Ministry 
visited the NIH in October 1981 to discuss 
closer cooperation in health. A draft 
agreement between the NIEHS and the 
Finnish Institute for Occupational Health 
was developed in FY 1981. 

• The U.S.-France Science and Technology 
Bilateral Meeting, which took place in 
Washington in September 1982. Under the 
framework of the science and technology 
agreement, the NIH has a cooperative pro- 
gram with INSERM. Current areas of active 
cooperation include cancer, respiratory 
diseases, and thyroglobulin synthesis. 

• The tenth meeting of the U.S.-Spain Joint 
Committee for Cooperation in Science and 
Technology, which was held in Washington in 
May 1982. This committee, a component of 
the Treaty of Friendship, provides for co- 
operation in science and technology with a 
recently added provision for health. 

• Two agreements signed under the overall 
cooperative science and technology agree- 
ment with Italy : (1) by the NINCDS, in 



25 



March 1982, for collaboration in neurosci- 
ences research with the National Research 
Council of Italy, and (2) by the NHLBI, in 
November 1981, for cooperation in cardio- 
vascular diseases with the Pharmacological 
Institute, University of Milam. In addition, 
in November 1981 under the science and 
technology agreement a workshop was held 
by the NIH in Bethesda entitled "Biological 
Response Modifiers," and a joint symposium 
by the NHLBI, "Methods of Noninvasive 
Diagnosis in Cardiovascular Disease." 

• The 3uly 1982 meeting of the Joint Com- 
mittee of the U.S.-3apan Cooperative Med- 
ical Science Program, in Tokyo at the Min- 
istry of Foreign Affairs. The 3oint Tuber- 
culosis Panels and 3oint Viral Disease Panels 
have begun a review that will be completed 
next year. After reviewing the Leprosy and 
Parasitic Disease Panels, the committee 
recommended their continuation. In the 
future, the Leprosy and Tuberculosis Panels 
will hold combined annual meetings in view 
of their common scientific interests, and 
the gxiidelines for the Joint Parasitic Dis- 
ease Panels will be updated to accommodate 
new technologies and changing needs. 

• The U.S.-Mexico meeting in Bethesda in 
December 1981, which resulted in an 
agreement between the PHS and the Mini- 
stry of Health of Mexico to collaborate in 
research and training in infectious diseases, 
particularly those of children. 

• The September 1982 visit to the United 
States by the Indian Prime Minister, which 
resulted in an agreement to establish an 
Indo-U.S. Blue Ribbon Panel to enhance 
science and technology cooperation between 
the two countries. Areas of interest being 
considered in the health field are leprosy, 
immunology, and blindness prevention. The 
ICL staff of the FIC work with staff of the 
Office of International Health and the 
Office of Science and Technology Policy in 
coordinating the programs at the NIH. 



Other Liaison Functions 

In addition to monitoring and assisting in 
bilateral activities, the ICL staff maintain 
liaison with WHO and PAHO and occasionally 
with other multilateral organizations, and they 
provide NIH positions on agenda issues for World 
Health Assemblies and PAHO and Western 
Pacific Regional Organization Directing Council 
meetings. ICL staff also provide material and 
support for NIH participation as an observer in 
meetings of the European Medical Research 
Council and process requests for services of NIH 



experts for WHO and PAHO committees and 
other purposes. 

The FIC is cooperating with PAHO in organ- 
izing and sponsoring a Workshop on Research 
Management Techniques for Latin American 
scientist administrators. The workshop, aimed at 
directors of large research institutions, research 
departments of major universities, and large 
public health laboratories, will be held in FY 
1983. 

The ICL staff assist the Institutes by review- 
ing and clearing foreign travel plans and by 
serving as a channel for cable communications to 
and from foreign embassies and the Department 
of State, by coordinating responses to inquiries 
on international issues, and by processing NIH 
foreign grants and contracts for clearance 
through the Department of State. 

The FIC Director meets periodically with the 
international programs representatives of the 
NIH bid's to exchange information and views on 
NIH international activities and to discuss im- 
plementation of related policies and procedures. 

Information on NIH international activities is 
collected and published in an annual report. 
Special reports are prepared and made available 
to NIH principals traveling to certain countries 
and to officials from other countries who visit 
the NIH. In addition, comprehensive briefing 
books on NIH activities with various foreign 
countries are produced. 

A special study underway in FY 1982 was a 
compilation of information on biomedical re- 
search institutions in China. The report, due to 
be published in FY 1983, will be available to all 
interested scientists and Government officials. It 
will contain names and locations of the insti- 
tutions, directors and laboratory chiefs, and 
recent publications from these institutions. 

Gorgas Memorial Laboratory 

The ICL staff also serve as the focus for U.S. 
Government core support provided through the 
FIC budget for the Gorgas Memorial Institute 
(GMI) of Tropical and Preventive Medicine, Inc., 
and the Gorgas Memorial Laboratory (GML) in 
Panama. In 1928, Congress authorized a perma- 
nent annual appropriation to the Gorgas Memor- 
ial Institute of Tropical and Preventive Medi- 
cine, Inc., Washington, D.C., for the operation 
and maintenance of a research laboratory in 
Panama. This action, together with land and 
building donated by the Government of Panama, 
permitted the establishment of the GML. Since 
FY 1971, the FIC budget has provided the annual 
U.S. core support funds, which amounted to 
$1.69 million in FY 1982. The FIC maintains 
general program oversight for this funding. 

The laboratory conducts a diversified program 
of research on tropical diseases, especially those 
endemic to Panama and neighboring countries. 
Particular emphasis is placed on virology, par- 



26 



asitology, and the effects of environmental 
change on disease vectors and transmission. Of 
late, it has also undertaken studies on other 
public health problems, e.g., cervical cancer and 
sexually transmitted diseases. In addition to 
research, it also provides special diagnostic and 
reference services, epidemic investigations, and 
surveillance of vector-borne diseases, and it 
conducts formal and informal research training 
for scientists and technicians from the United 
States, Panama, and other countries. It has co- 
operative arrangements with several U.S. uni- 
versities for graduate and medical students. 
Formal training courses in tropical medicine are 
conducted several times a year for U.S. Navy 
medical officers. For FY 1982, the GML had a 
number of substantial scientific accomplish- 
ments in the following areas: 

• Ecology . The Bayano environmental eco- 
logical studies indicated significant alter- 
ations in insect vectors and disease poten- 
tial in the area. Yellow fever surveillance 
among monkey populations in the moun- 
tainous areas of eastern Panama indicated a 
resurgence of syl vatic yellow fever beyond 
last year's limits. A manuscript on the 
mammalian fauna of Panama was com- 
pleted, and extensive progress has been 
made on a compilation of the rodents of 
Panama. Studies describing how excessive 
hunting, massive deforestation, and other 
ecological problems have contributed to the 
disappearance of a number of valuable ani- 
mal and plant species have resulted in rec- 
ommendations for conservation of natural 
resources. 

• Vector Biology . Work in this area has ex- 
panded markedly. Currently 255 animal and 
avian species have been bled in the prepar- 
ation of antisera for blood meal analysis. 
Over 7,000 hemotophagous arthropods rep- 
resenting 17 genera and 88 species of sand- 
flies, mosquitoes, triatomes, and culicoides 
from Central and South America have been 
studied. Further study of lutzomyia sand- 
flies and of man-biting black flies ( simulium 
quadrivittatum ) has enabled GML scientists 
to characterize these disease vectors fur- 



ther, a step necessary to future vector 
control efforts. 

• Epidemiology . An epidemic of acute hemor- 
rhagic conjunctivitis, which occurred in 
Colon in 1981, was subject to a detailed 
seroepidemiological study. A 53 percent 
clinical attack rate was found, as well as 
information on the effect of socioeconomic 
level, crowding, and other parameters. A 
preliminary serological study indicated 22 
percent of the individuals tested had anti- 
bodies for HTLV, the highest known anti- 
body rate for HTLV. Further studies are 
planned in collaboration with the NCI. 
Haemagogus equinus mosquitoes have been 
studied for their efficiency as a vector of 
yellow fever. Studies have shown that St. 
Louis encephalitis virus transmission is an 
annual occurrence at two ecologically dis- 
tinct sites in Panama, a finding that sup- 
ports field data implicating the two-toed 
sloth as a host for the St. Louis encephalitis 
virus. 

• Parasitic Diseases . Drug evaluation in the 
Aotus monkey revealed two agents with 
significant antimalarial activity. Success in 
maintaining Plasmodium vivax for 10 days 
with one subculture was recorded. Field 
study in Morti, Darien Province, indicated 
an endemic focus of Mansonella ozzardi 
probably transmitted by simuliid flies. 

• Bacteriology . Further studies on Campylo - 
bacter jejuni in childhood diarrhea indicate 
a high incidence in the first 6 months of 
life. Antibody resistance to strains of Shi - 
gella and the emergence of several new 
strains have been documented. Penicillin- 
resistant strains of gonococci were encoun- 
tered in 12 percent of 377 prostitutes ex- 
amined. 

The GML is being reorganized to emphasize 
tropical ecology, epidemiology, microbiology, 
and clinical therapeutics. This reorganization, as 
well as the consolidation of facilities, will enable 
the GML to maintain a productive research 
program. 



27 



Chapter IV 
National Cancer Institute 



The international battle against cancer offers 
perhaps the best and most immediate oppor- 
tunity for changing the basic quality of life for 
millions of people throughout the world. The 
National Cancer Institute (NCI) continues to 
contribute readily to the improvement of that 
quality of life because of its long tradition of 
involvement in the international arena for can- 
cer research. Although self-interest, on behalf of 
the people of the United States, motivated NCI's 
irutial concern with cancer problems in other 
nations, this self-interest has been trans- formed 
into a concerted international campaign in the 
war on cancer. The National Cancer Act 
intensified the commitment of the NCI to the 
international team approach toward the control, 
prevention, and ultimate eradication of cancer 
as a major crippler and killer disease of a large 
segment of the world's population. 

By virtue of an international effort, striking 
geographic and environmental variations in the 
incidence and mortality of a wide range of spe- 
cific organ cancers are now well recognized and, 
in some instances, environmental causes have 
been established for excess rates of cancer in- 
cidence in certain regions of the world. For 
instance, environmental factors are implicated 
in the causation of a large percent of the known 
cancers. The derivation of this cause-effect 
relationship stems from studies in those coun- 
tries of the world where the population is at low 
risk for a given type of cancer, thereby estab- 
lishing a "baseline" rate for that particular can- 
cer type. Subsequently, a high rate of incidence 
for that same cancer in other countries can be 
assumed to be associated with environmental 
factors. That the incidence of various types of 
cancer exhibits great geographic variation is 
illustrated by differences in the rate of lung 
cancer incidence among men in Scotland, the 
United States, and Portugal. Scotland, with the 
highest rate in the world, has twice the rate for 
U.S. white males, whereas the rate among Por- 
tuguese males is one-seventh that of Scotland. 
Again, in the Kazakh Republic of the U.S.S.R., 
the incidence of cancer of the esophagus is ex- 
tremely high in regions near the Caspian Sea in 
comparison to the low incidence in the extreme 
eastern section of that Soviet republic. 



Through its participation in activities of the 
international cancer science community, the NCI 
benefits from rapid advances in basic research 
throughout the world and application of this new 
information to the clinical management, control, 
and prevention of cancer. The ultimate gain 
from such collaborative cancer research efforts 
of the NCI and international counterparts is a 
tangible improvement in the quality and quantity 
of health services available to millions of people 
over the world. 

The contribution of the NCI to the interna- 
tional struggle against cancer includes: (1) con- 
tinuing support of cancer research in foreign 
countries by highly qualified scientists; (2) sup- 
port of cooperative research programs, princi- 
pally under bilateral agreements with foreign 
governments, institutions, or organizations; (3) 
maintenance of liaison and research collabora- 
tion with international organizations and agen- 
cies that have well-defined objectives in cancer 
research and cancer prevention; W support of 
training of foreign scientists in the United States 
as well as of the interaction of American sci- 
entists with colleagues in foreign laboratories; 
and (5) management and operation of an Inter- 
national Cancer Research Data Bank for pro- 
moting and facilitating, on a worldwide basis, 
the exchange of information for cancer research, 
care and management of patients, and cancer 
control and/or prevention. 

Summan of International Programs 
and Activities 

Bilateral Agreements and Other 
Countn-to-Countn Activities 

Cooperative cancer research programs under 
formal government-to-government treaties and 
other forms of bilateral agreement constitute a 
major segment of the international activities of 
the NCI. The first of these cooperative cancer 
research agreements was established May 23, 
1972, with the signing of the U.S.-U.S.S.R. 
Agreement for Cooperation in the Fields of 
Medical Science and Public Health. Subse- 
quently, additional bilateral programs were 
formalized between the NCI and the Japanese 



28 



Societ)- for trie Promotion of Science (197ft); the c: I'zz'—z.-.z- 

Institute of Oncology, Warsaw, Poland (197^), ce.e.:;--e-: 

under the U^.-Polish People's Republic Agree- esr:e-c.i.. :-: 

m«it; in 1975 with INSERM, under ar. earlier -~f.zi- -..-z 

NIH agreement with LNSERM; the Cairo Career ca-c-.-es a.-c : 

Institute (1976), under the aegis of the agree- c:ag-:s.s- s:=.; 

ment between the L'ritec States a-t t-.e Ara:: e$:t"a.ze=.. l*: 
Republic of Egypt; the '.'.l-.str. :: Sc.er.-ce ar.c 

Technology of the Fecera. -et-olic of Ger-r.any • "-: :.-t rese 

(1976); the Ca--e- :-st.:.:e Hospital), Chinese a res..: t: . 

Academy of ''ec.ta. 5:.e-ces, under the U.S.- .31'.. z^.-^^- 

P.R.C. Accorc for CccDeratic- Ir Scierce ar.c a-t '..s c:.-=: 

Technology (1979); tre'sCI c: V.i-ar. a-.c t-.e l-s:.:.:e -zr, 

Institute of Oncolog>- zi C-e-.oa^ Italy ilSiZ}-. ar.c bioc.--r-.ta. t: 

the National Institute of Crcclcsv, Bucat^est, live.- ta-:.-:z 

Hungary (1981). ' e::et:s :: ta": 

The following sect:t-s test-.te NCI ci^atera. 
activities and the prcgress :-at ras oeer. ~.ace • -- et.tr-.:. 

through these cooperative efforts. f-:- fr ce. . 



Z. .i. 



China -a. Ia-:e- ;-5:.:-:r :a-t.;.ta:r: .- a 1- 

wee.< N i; -:-•$■:: r-:.:.ec £p-ce— .:.:;• 

Bera.'een ranuar>" 1, i9Sl. arc Cctcce.- 31. of T Ce,. _--;-:-as t- z Lr_xe— .las, -s a 

1982, seven American scientists visitec ^-.stl- result cf t-esa tztzti, a ~._tlc.s-cl- 

tutes in Chma to hold cc~s-lt = tlc-.s. tc p-ese-t plLnary researc" f: e:: .s .-te- t:-:.ter- 

lectures, to provide tec---:.:z;- ce- :-s:-a:.:-5, ation for imple- e-:a:.;-, ;e-t.-z -ert.:: ;: 

a-t. gsneraliy, to enhance tne exc-a-ge :: :a:a sc~e accltlc.-a. cata frcf. tne ~--_-as-e s.ce. 
a-c .--Jior-nation on cancer researc" ::p.t: :: 
mutual interest and benefit. Reclprcca^iv, seven • .-. cc-fa:: ::.- -ea!. :...:,. 5:.:.e$ ::r Ic- 

stucy/research progra~s a-.c 5:. = -:.:.: -:.-<- Z'-'t "as trf -agct.atet z^'.-ir:- :-e NCI 

shops at tn« NCI anc other .-.— er.ca- cancer anc tne Ca,-car l-;t.t_:e -:5:.:a. .- =r.- 

centers. Tnese exchanges have effectively f_r- -L-g. ~-e -esea.-cn act.v.:.e; :: re ::-:-::r: 

thered the development and l.~.pie~e-: = tlcn cf 1- Z-^-a .-:..:a; a -.:.■.:.:- .-:e.- ■ e-:.:- 

joint research activities on cancer p-:c.r — 5 :f tr.a- a'c case-cc-t::. st.C; :: escfagaa. 

mutual interest, with a n^ntber of :-a--a.5 :: cancer 1*. LL-.x.a-., a caia-ccn:-:. st.:- of 

communication and a variety of — ec-an^s-ns Ln lung :a-: 

use. stwC :: 



- N - : 



jjng, w.t- 5.:se:-a-: a cas.:- :: :.- 

Coliabcratior, 'jnder .ArLnex Two of the Health areas cf .■_£■ .-cca'ca a.--c -crta—tj _". 

Protocol .— ?_r5_a-t tc tne prcv:s.cns cf .-.--ex Chi-.a. 

Two, the NCI recelvec r- c ec.ce—.ic.ogists, eacn 

for 1 year of st.cy ressa-c".. .-. t-irc Cnl-ese • .An c-tgrc-n- cf sc.a-:.:.c axc.-an.ges c_r..ng 

specialist, an enccsccp.s: c.ag- :::.c.a-. ca-a a .ate .fS. a-c -.c-.-il ■visit by an NCI- 

for 1 year of observation a-c e.\par.a-ce .- :-e rrr-sr-ec -_:-.:.:-.:: r.rc-e—lr: --a^ a 

clinics and laboratories of se.ectac -~e-.z = ~. zzzz^i. :: 5:.: -.-e aila:: :: :.a:ar>- 

cancer centers. sa.e-^.- a-: ::-a- vara a.a-a-ts c" ca-- 

The Cancer Instirote (Hcsp.ta. , ra. .-g, - ai 
the coordinating focus for the activities of two 
NCI scientists, each for i .month of exc-a-ges, 
relating to the subject of early detect.:- a-c 
diagnosis of cancer. 






; A ^ - — 



Direct Interinstitute coUaboratlo-n (o-tslde of bot- 

the Annex) .— T-Is apprcac-- e-cT-7ec cv t-e — e-.t 
Progra— CocrcLnatcrs. nas per— .::ac acc.:.:-a^ 

scientific excnanges and project ca-a.cc — e-t. 2_rl-.g 






*^ — A2 



• Two .^n-.erica- specialists in anticancer cr_g nese sc.5-:.s:5 ::■ ;:-:■ -asaa-;- .- ~:.a:_.ar 

develoD~.ent and evaluatio-. c-e f'c~ fa clclct'. c._--ca. .ar:"a:c'- ic.a-ca, z~ z Zss-c^r 

NCI anc one from th a '■'.:-- -a". ca- Ca-car cetac:.:" a-c :.ac-:;-5. .-.ace-;:!.. . :-e NCI 

Ce-ta' 1- Ka-sas, \'. sitae C-.-asa ca"cer - „. sa-c 5C-.a-t.;t5 ■; : T-.-a ::" : ;..accratlve 

anc p -a"~acewt.cai Lnst-t^tas fcr exc~a-.£a st-c.as re.latec tc aa.-.- ca'.act.:- a"c cias.nosis 



and to epidemiologic research. Areas considered 
o be of significance and mutual benefit include 
identification and characterization of biochem- 
ical/biologic markers of tumors, unified concepts 
for the collection and analysis of epidemiologic 
data, photoimaging and intensification in de- 
tection/diagnosis, exploitation of the utility of 
photoradiation therapy, and studies related to 
genetic predisposition or susceptibility to cancer. 
The joint research efforts initiated as direct 
interinstitute activities will continue. Other such 
initiatives will be considered on a research pri- 
ority basis, for instance, studies on automated 
cytology and dietary factors and their role in 
carcinogenesis and/or in cancer chemopreven- 
tion /intervention. 

Egypt 

The Cairo Cancer Institute, a well-organized 
facility, has an accrual of patients with bladder 
cancer perhaps greater than that of any other 
single institution in the world. Recently, a Phase 
II study of chemotherapeutic agents for bladder 
cancer was completed, having been initiated in 
1976. Twelve drugs were studied in about WO 
patients with squamous and transitional cell 
bilharzial bladder carcinoma. The preparations 
studied included hexamethylmelamine, VM26, 
methotrexate, bleomycin, adriamycin, platinum, 
Cytoxan, fluorouracil, trenimone, m-AMSA, 
vincristine, and pentamethylmelamine. Notable 
response rates were 38 percent for hexamethyl- 
melamine, W percent for pentamethylmelamine, 
^'t percent for vincristine, and 60 percent for 
trenimone. The response rates for Cytoxan, 
fluorouracil, and DDP are, respectively, 28 per- 
cent, 15 percent, and 13 percent. 

On the basis of these results, an active chem- 
otherapy combination might include vincristine, 
pentamethylmelamine, and fluorouracil. The 
durable response rate after radical cystectomy 
in bilharzial bladder carcinoma is 35 percent 
(5-year disease-free survival), not improved by 
pre- or postoperative radiotherapy. The com- 
bination described above is under active con- 
sideration as are other combinations of drugs. It 
is anticipated that 100 patients can be entered 
on each arm of a two-armed randomized study 
within 2 years. The drugs would be made avail- 
able by the NCI for this latest study under the 
U.S. -Egyptian program. 

France 

Two broad areas of cancer research now con- 
stitute the cooperative activities between 
American and French cancer specialists. These 
are a basic cancer research program area and a 
clinical cancer research program area. Activities 
constituting the basic area include biologic and 
chemical carcinogenesis, cellular and molecular 
biology, viral oncology, cancer immunology, and 



hormone research related to cancer. In March 
1982, during a review and evaluation meeting, 
American and French collaborators agreed to 
continue the research programs that have been 
established and show promise as well as to stim- 
ulate new ideas and support the exchange of 
scientists for information and active research 
collaboration. Thus, five American investigators 
subsequently spent periods ranging from 2 weeks 
to 6 months in French laboratories for collabo- 
rative studies in hormone and receptor research, 
nucleic acid metabolism and alteration, muta- 
genesis, and carcinogenesis. Reciprocally, four 
French investigators worked in American lab- 
oratories on research problems related to gene 
expression, hepatitis virus antigens, viral on- 
cology, and antiviral interventions in certain 
types of cancers. 

In Paris, in June 1982, the joint American- 
French Committee for Clinical Cancer Research 
met to review the progress that had been made 
in that area as well as to plan the program for 
the subsequent year. They assessed cooperative 
research endeavors in the clinical study of breast 
cancer treatment, the treatment of osteosar- 
coma, biochemical and clinical pharmacology, 
and hormone therapy used in breast cancer. An 
American epidemiologist spent 6 months col- 
laborating with French investigators on biosta- 
tistics and clinical epidemiology. An American 
endocrinologist spent 2 weeks in France con- 
ferring with experts on the biochemical effects 
of estrogens in endometrial cancer, while a 
French pharmacologist came to the United 
States to receive advanced training in biochem- 
ical pharmacology so that he could establish a 
collaborative research program with his Ameri- 
can colleagues upon his return to France. 

Federal Republic of Germany 

In the environmental carcinogenesis program 
area, an epidemiologist from the German Cancer 
Research Center in Heidelberg visited the NCI 
to exchange information on analytic epidemiol- 
ogy and to engage in a case control study of 
occupational epidemiology related to workers in 
certain hazardous occupations. He was able to 
accrue experience in the conceptual aspects of 
epidemiologic investigations, data analysis, and 
the implementation of studies in the network of 
surveillance and monitoring. Based on his ex- 
changes in the United States, at the NCI and 
New York University Medical Center, he and his 
German colleagues are involved with American 
counterparts in the development of joint epi- 
demiologic studies of workers in the chemical 
industry. Included in the joint effort will be the 
establishment of a system for cancer registry. 

A German pathologist came to the NCI to 
conduct joint studies aimed at developing a 
common system of classification and terminol- 
ogy related to experimental cancers and tumors 



30 



so that a comparable system could be established 
in the NCI and the German Cancer Research 
Center in Heidelberg. Thus, an exchange of 
materials and specimens for comparative studies 
between the Federal Republic of Germany and 
the United States will now be possible. 

Hungary 

Three American immunologists visited Buda- 
pest to attend a course, "Highlights in Modern 
Immunology," sponsored by WHO and the Hun- 
garian Society of Immunology. The course, con- 
sisting of lectures delivered by members of the 
Hungarian Society and other internationally 
renowned scientists, addressed topics relevant to 
immunogenetics, immune receptors, effector 
functions and their regulation, and differenti- 
ation. The lectures were aimed at young scien- 
tists and were, therefore, broad in nature. The 
consensus of the Americans was that, in general, 
the Hungarian immunologists with whom they 
Interacted were impressive and that these Hun- 
garian scientists appeared to be very eager to 
continue and to further expand the scientific 
exchange of information with Americans. 

An intramural NCI scientist spent 2 weeks in 
Budapest participating in exchanges of infor- 
mation on theoretical and practical concepts in 
pathology and cancer data processing. As well, 
he hoped to determine if the methods of pathol- 
ogy data processing used in Hungary have ap- 
plication in the United States. 

An experimental chemotherapist from the 
National Institute of Oncology, Budapest, spent 6 
months in the NCI Laboratory of Medicinal 
Chemistry and Biology engaging in studies de- 
signed to investigate the resistance of murine 
tumor cells to alkylating agents used as anti- 
cancer drugs. Her work and that of her NCI 
colleagues have confirmed the role of the tri- 
peptide glutathione in resistance of tumor cells 
to alkylating agents. These studies have demon- 
strated that it is possible to sensitize the re- 
sistant cancer cell completely to the cytotoxic 
effects of an anticancer drug such as L-phenyl- 
alanine mustard, commercially known as Mel- 
phalan. Melphalan is one of the effective drugs, 
used in combination with others, for the treat- 
ment of breast cancer. Additionally, the chemo- 
therapist devoted considerable effort toward the 
development of amino acid specific, synthetic- 
pelleted diets for use in these experiments. She 
contributed significantly to the evaluation of an 
Alzet osmotic minipump for continuous intra- 
peritoneal infusion of agents such as buthionine 
sulfoxime (an inhibitor of glutathionine biosyn- 
thesis) and anticancer agents, thus affording a 
concentrating effect of antitumor agent at the 
site of the cancer. 

A transplantation biologist/tumor immunolo- 
gist from the National Institute of Hematology 
and Blood Transfusion, Budapest, spent 't months 



in the Sidney Farber Cancer Institute (SFCI). He 
devoted his efforts there to joint research on 
developing monoclonal antibodies active against 
T cells and monocytes in endothelial cells (EC). 
His approach was to collect endothelial cells 
from the umbilical cord and to enmass the an- 
tigens acting against the monoclonal antibodies. 
Based on his research, he concluded that EC are 
rich in their expression of HLA-A, B, and C 
antigens but that their expression of HLA-DR is 
anomalous. EC also share myelomonocytic sur- 
face antigens, My-7, Mo-3, and Mo-^. The rele- 
vance of these findings to transplantation is 
enhanced by initial observations that Mo-'^ is 
also expressed in human kidney endothelium as 
shown by immunoperoxidase reactions. The re- 
searcher became acquainted with the method for 
phenotyping leukemic cells by means of mono- 
clonal antibodies and, by virtue of an SFCI gift 
of a series of monoclonal antibodies, he has 
begun phenotyping leukemias and lymphomas in 
his laboratory in Budapest. Because of the SFCI 
interest in the Hungarian study on HLA-antigen 
distribution in gypsies and in the incidence of 
various diseases in this ethnic group, the Hun- 
garian scientist has provided SFCI scientists with 
more than 30 blood samples of Hungarian gypsies 
for typing the complement phenotypes. 

An experimental pathologist/chemotherapist 
from the Semmelweis Medical University in 
Budapest spent 6 months at the Roswell Park 
Memorial Institute to study methods of tumor 
disaggregation—mechanical and enzymic — to 
yield single cancer cell suspensions. At the same 
time, he developed cell separation methodologies 
for biochemical, biologic, and morphologic 
characterization of the various tumor subsets 
derived from the human tumor cell suspensions. 
The subsets, then, were tested for their sensi- 
tivity to anticancer drugs. Among 17 tumor cell 
types studied, there were significant differences 
in the number of cells obtained by disaggrega- 
tion. In six cell fractions, intracellular concen- 
tration of the anticancer agent, Ara-C, and 
-^H-thymidine was higher in the fractions 
containing more viable cells. The effect with a 
platinum-derived drug was the opposite, in that 
results suggest an intensive binding to nonviable 
cells. 

Italy 

Activities in cancer therapeutics and cancer 
prevention constitute the efforts of collabo- 
ration between American and Italian cancer 
specialists. 

During the annual review meeting for the 
cancer therapeutics program, held in Bethesda, 
Maryland, in November 1981, there was a de- 
tailed exchange of information in the areas of 
clinical trials, basic and clinical pharmacology, 
and cancer related epidemiology. Until now, the 
need to establish a foundation for a collaborative 



31 



project in bicx:hemical pharmacology, breast 
cancer treatnnent, pediatric oncology, cancer 
naetastases, clinical trials with anthracyclines, 
radiation oncology, and biologic response modi- 
fiers has motivated the joint workshops and 
symposia. In the next year, it is anticipated that 
specific joint projects in clinical and preclinical 
cancer research will be defined. 

Two American pharmacologists from the Ros- 
well Park Memorial Institute visited Italian 
research centers to discuss and plan collabora- 
tive research on the study of modal systems for 
investigating drug metabolism and to obtain the 
most recent information on the anthracycline 
drugs being tested and used in Italy. 

From the Italian side, a pediatric oncologist 
observed the methods of treatment for childhood 
cancer in cancer centers of the United States. 
Another pediatrician spent 2 months at the NCI 
to participate in a study of Phase I and II drugs 
being used to treat solid tumors and acute lym- 
phoblastic leukemia in children. He was also a 
benefactor of the latest information on dose- 
limiting toxicity and antitumor activity of those 
drugs being used currently to treat bone sar- 
comas, neuroblastoma, and other childhood can- 
cers. An immunologist from Italy spent 2 months 
at the Frederick Cancer Research Facility to 
study the utility and physiologic effects of bio- 
logic response modifiers currently in use to treat 
cancer. Advanced training in biochemical phar- 
macology and experimental chemotherapy was 
the goal of a young Italian oncologist who spent 
1 year of study /research at the Roswell Park 
Memorial Institute in Buffalo, New York. 

The annual review meeting for the cancer 
prevention program took place in conjunction 
with the "Workshop on Leather, Benzene, and 
Shipyard Workers," which was convened in Por- 
tofino, Italy, in 1981. The workshop was devoted 
to discussions on the development of collabo- 
rative studies for identification of environmental 
determinants of specific cancers. Unique op- 
portunities exist in Italy to assess the impact of 
certain occupational exposures, particularly 
benzene, chromates, and dusts in the leather and 
shoemaking industries. Attention was focused, as 
well, on the risk of lung cancer among shipyard 
workers. 

An Italian viral oncologist spent more than a 
year at the Mount Sinai Medical School in New 
York to study the relationships between polya- 
mine biosynthesis and differentiation in an at- 
tempt to elucidate the biologic role of these 
compounds in the steps leading to differentiation 
of the erythroleukemia cells. 

An Italian biochemist spent 3 months at the 
M.D. Anderson Hospital and Tumor Institute in 
Houston, Texas, to learn techniques for the 
detection of alterations in DNA induced by car- 
cinogens. As a result of this interaction with his 
colleagues, this researcher participated in 



devising plans to continue the collaborative 
studies initiated on the differential and system- 
atic enzymatic digestion of DNA and on the sep- 
aration and analysis of the subsequent DNA 
fragments. 

3apan 

At the outset of the agreement between the 
NCI and the Japanese Society for the Promotion 
of Science, 11 specialty areas in cancer research 
were pursued jointly. Three years ago, these 
were categorized into four broad program areas, 
namely, etiology, cancer biology and diagnosis, 
cancer treatment, and interdisciplinary research. 

Cancer epidemiology, chemical carcinogen- 
esis, viral and biologic carcinogenesis, and mo- 
lecular biology constitute the principal areas of 
research being pursued under the etiology pro- 
gram. The principal objectives are to clarify the 
cause of human cancers and to determine the 
mechanism(s) of carcinogenesis. 

During the course of a seminar entitled "Car- 
cinogenesis and Gene Expression in Liver Cell 
Cultures," held in Hawaii in November 1981, 
information was exchanged on the patterns of 
expression of various genes during carcinogen- 
esis, especially hepatocarcinogenesis. Data pre- 
sented at the seminar indicated that changes in 
the expression of various genes were reflected 
by the production of enzyme systems and other 
proteins that were not found in the normal liver 
celL The change is so pleiotropic that the mech- 
anisms of some of these changes would be in- 
trinsically relevant to the carcinogenic process. 

Many aspects of intestinal metaplasia were 
considered during a conference titled "Intestinal 
Metaplasia and Stomach Cancer," convened in 
Shimodu, Japan, in March 1982. New histologic 
and biochemical enzymatic techniques were 
considered as were new methods for histochem- 
ical and immunologic assays. An interesting 
finding emerged with bearing on the relationship 
between mesenchymal and epithelial tissue, 
namely, that stroma can influence and guide the 
development of epithelial tissues. Although there 
was no consensus on whether intestinal meta- 
plasia is a precursor lesion for stomach cancer or 
only an associated condition, some investigators 
believed that a definite precursor relationship 
could be demonstrated. Since the cause of 
stomach cancer is complex, it is reasonable to 
expect that some stomach cancers can be form- 
ed by a process not related to the formation of 
intestinal metaplasia. 

A conference entitled "Cell Interaction and 
Cancer," held in Kyoto, Japan, in November 
1981, was one of the focal activities in the can- 
cer biology program area. Information was 
exchanged between American and Japanese 
counterparts on a diverse series of topics ranging 
from cell-to-cell adhesion in primitive cell 



32 



systems to studies of the pathology and biology 
of human cancer cells. Highlighting the discus- 
sions was the study of differentiation of tissue 
mast cells and the growth of leukemia cells in 
microenvironments; cell-binding sites of colla- 
gen, heparin, and other macromolecules; and 
regulatory proteins on transformed cells. 

In another activity in this program area Amer- 
ican and Japanese immunologists convened a 
meeting in Boston in November 1981 on the 
analysis of mechanisms for induction of tumor- 
specific immunity and experimental approaches 
to tumor immunoprophylaxis and therapy. The 
participants focused their attention on the anti- 
genic nature of tumor cells, expression and reg- 
ulations of tumor antigens, fundamental immu- 
nologic processes in host response to tumors, and 
preclinical applications of tumor immunology. 

Hakoni, Japan, was the site in March 1982 of a 
meeting on the application of cytology automa- 
tion in cancer cytology and cell biology, as a 
component of the cancer diagnosis program area. 
American and Japanese investigators discussed 
the latest information on instrumentation and 
data analysis, the application of automated 
cytology technology in cell biology, a new tech- 
nologic approach for sample preparation, and the 
application of automated cytology in cancer 
detection. 

It was a particularly active year in the cancer 
treatment program area in which three meetings 
were convened. The first, the Seventh Annual 
Program Review Meeting, related to develop- 
ment and evaluation of treatment of cancer with 
combined modalities of therapy. The conferees 
were concerned with three topics: treatment of 
oat cell carcinoma of the lung in the United 
States and Japcin; development of new method- 
ology in clinical and preclinical investigations, 
including the progress of human tumor cloning 
assay as a predictor for the sensitivity in situ of 
human tumors to administered drugs; and new 
antitumor agents, natural and synthetic, now in 
Phase I and II as well as those still in preclinical 
stages of development. 

The second assembly in this program, which 
took place in October 1981 in Maui, Hawaii, was 
the first meeting on preclinical and clinical 
trials of tumor immunology. Subjects for infor- 
mation exchange included experimental studies 
of cancer immunotherapy, possible application of 
human T cell hybridomas for immunotherapy of 
cancer, monoclonal antibody therapy in man, 
adjuvant immunotherapy of lung cancer with 
bacterial cell wall skeleton preparations, current 
status of interferon therapy, and clinical trials 
using immunotherapeutic approaches. 

The third meeting, held in Tokyo in November 
1981, concerned advances in the treatment of 
bladder cancer. Topics for information exchange 
were superficial cancer of the bladder, deeply 
invasive cancer of the bladder, metastatic 



disease, prevention of bladder cancer, conduct of 
clinical trials, and projected cooperative bladder 
cancer treatment programs. In general, the 
exchanges served as a foundation for further 
cooperative studies of bladder cancer as well as 
basic and clinical investigations on bladder can- 
cer. In addition, criteria for diagnosis and for 
development of protocols were established, 
which will be useful to investigators in both 
countries for facilitating the mutual under- 
standing and use of diagnostic, therapeutic, and 
clinical technologies. 

In Hawaii, in March 1982, a seminar entitled 
"Neural Crest Tumors" represented a key ac- 
tivity in the interdisciplinary program area. 
During the session, attention centered on certain 
syndromes associated with tumors or familial 
neoplasia derived from the neural crest and on 
differences between the frequencies of these 
tumors in both countries. 

American and Japanese viral oncologists, 
pathologists, and epidemiologists assembled in 
Seattle, Washington, in March 1982 to discuss 
the nature of T cell leukemias and their probable 
etiologic agents. During this symposium entitled 
"T Cell Leukemia/Lymphoma—Role of Human 
Type C Retroviruses," it was learned that teams 
of American and Japanese virologists had inde- 
pendently isolated and identified retroviruses 
associated with HTLV and ATLV, respectively. 
These newly identified human retroviruses seem 
to be identical or very similar to each other. The 
viruses are closely associated with mycosis 
fungoides, Sezary syndrome, and adult T cell 
leukemia that belong to the category of dif- 
ferentiated T cell lymphoma and leukemia. The 
viruses have been found to be endemic in the 
southwestern part of Japan and in certain Car- 
ibbean islands. 

Related to the foregoing, an American path- 
ologist visited several Japanese laboratories to 
review information and to plan cooperative 
studies on leukemias and lymphomas. Recipro- 
cally, a Japanese scientist came to the United 
States to visit cancer centers for the study of 
the classification of lymphomas. Another Jap- 
anese, an immunologist, spent his time studying 
methods for jn vitro sensitization and testing of 
cytotoxic lymphocytes. 

Poland 

Exchange of scientists between the Polish 
People's Republic and the United States has 
continued to be effective, despite the current 
political climate in Poland. 

An American pharmaceutical chemist spent 6 
weeks at the Institute of Oncology in Warsaw to 
conduct collaborative studies in nuclear medi- 
cine and radiopharmaceutical research. With his 
Polish counterpart, he investigated the possi- 
bilities of using microspheres as carriers of 



33 



radioactive isotopes for treating certain types of 
cancers such as hepatic carcinoma. The experi- 
ments demonstrated the stability of microsphere 
carriers in animal models as well as the potential 
for the use of such agents in treating cancers in 
humans. 

During the year, six Polish scientists visited 
the United States to do research in their spe- 
cialties. The first, a tumor biologist, visited 
centers of excellence in the United States to 
exchange information and learn of recent ad- 
vances in radiation biology, cancer immunology, 
and biology. A biologist from the Institute of 
Oncology in Warsaw spent 6 months collabora- 
ting on DNA polymerase research at the Roche 
Institute of Molecular Biology. A Polish bio- 
chemist came to do research on chemical car- 
cinogenesis. A pharmacologist spent his time in 
collaborative studies of biochemical pharmacol- 
ogy and tumor immunology at the Roswell Park 
Memorial Institute. 

The director of the Institute of Oncology in 
Warsaw, after attending the 13th International 
Cancer Congress in Seattle, Washington, visited 
cancer centers in that area, as well as others in 
the United States, for discussions on the progress 
and achievements of the Polish National Cancer 
Program as well as the accomplishments under 
the U.S. -Polish People's Republic Cooperative 
Cancer Program. Finally, a pediatrican from the 
Nation Research Institute of Mother and Child in 
Warsaw observed and studied treatment modal- 
ities and procedures for childhood cancer in the 
Pediatric Oncology Branch of the NCI. 

U.S.S.R. 

The six original program areas ~ in effect 
since inception of the U.S.-U.S.S.R. Health 
Agreement in 1972 ~ were modified, restruc- 
tured, and/or merged during the Sixth U.S.- 
U.S.S.R. Meeting on the Problem of Malignant 
Neoplasia, held in Bethesda, Maryland, Septem- 
ber 1981. Thus, the scientific areas of cancer 
treatment, carcinogenesis, and cancer preven- 
tion now constitute priority areas for continuing 
collaboration between American and Soviet 
cancer specialists. 

An NCI intramural scientist, during his No- 
vember 1981 visit to Moscow's AU-Union Onco- 
logic Scientific Center, was able to engage in 
productive discussions on cancer chemotherapy, 
especially from the view of detailed analyses of 
raw data and participation in clinical rounds for 
the observation of Soviet patients entered into a 
parallel study of tamoxifen as an adjuvant in the 
surgical treatment of breast cancer. Preliminary 
data indicate positive treatment results with this 
agent, and the patient accrual under the study 
should yield promising information regarding this 
mode of treatment. The NCI provides the ta- 
moxifen and research counsel for this parallel 
study. 



3^ 



The NCI has been provided with additional 
quantities of the Soviet drug known as histar, for 
completion of preclinical testing in xenograft 
systems following demonstration of positive 
histar activity in L-1210 leukemia, B-16 mela- 
noma, and CD8f mammary tumor. The Soviets 
are also preparing samples for NCI testing of 
three compounds of natural origin and their 
indication of potential use as anticancer agents. 
These are bacuchiol, an antibiotic, and chrys- 
ophanol and cynodontin, which are lichen 
products. 

During their January-February 1982 visit to 
the NCI and other U.S. cancer centers, two 
Soviet chemotherapists joined American col- 
leagues at the University of Maryland Cancer 
Center to design and develop a protocol for a 
"Phase I Clinical and Pharmacologic Trial of 
Platinum diammine (1,1-cyclobutane-dichlor- 
oxyIate)2-(-0,0')." The agent is commonly re- 
ferred to as CBDCA. Paralleling the study of the 
American scientists and clinicians, the Soviets 
will pursue (1) establishing the maximum human 
tolerable dose of CBDCA; (2) evaluating its 
toxicity in patients with previously treated and 
untreated malignancies; and (3) researching its 
antitumor activity and its clinical pharmacoki- 
netics. The pharmacologic committee of the 
U.S.S.R. Ministry of Public Health approved the 
use in Soviet patients of CBDCA, which has been 
provided to the U.S.S.R. scientists by the NCI. 
Evaluation of the protocol is underway in the 
U.S.S.R. as well as in the United States. 

From May 23 to June 6, 1982, a medicinal 
chemist from the University of Michigan was in 
the U.S.S.R. to participate in a meeting on drug 
design and bioorganic chemistry as well as to 
meet with colleagues in a variety of institutes 
for discussion of drug development and design, 
advances in bioorganic chemistry, and organic 
and medicinal chemistry. He returned with 
abundant information from Soviet colleagues on 
progress they have made with a number of 
alkylating anticancer compounds as well as 
adamantane derivatives, some vinca compounds, 
and glycopeptide preparations such as the Soviet 
agent known as khanerol. 

A microbiologist from Pennsylvania State 
University spent 2 months in the U.S.S.R. pur- 
suing joint experiments on "Herpesvirus Papio: 
Modulation of Virus Expression in Baboon Lym- 
phoma" at the Institute of Experimental Path- 
ology and Therapy, Sukhumi, Georgian S.S.R. The 
Sukhumi Center is perhaps the largest facility in 
the world for primates in captivity. In general, 
the scientific benefit to American scientists is 
accessibility to this large colony of baboons and 
other primates. These animals have been a val- 
uable resource for isolating primate retroviruses, 
isolating primate herpesviruses and determining 
their role in the development of certain lympho- 
proliferative diseases, and identifying genetic 
factors resulting from inbreeding. 



After their participation in the 13th Interna- 
tional Cancer Congress in Seattle, Washington, 
two Soviet chemotherapists spent an additional 3 
weeks in the United States visiting centers of 
excellence related to the studies they are pur- 
suing jointly or independently. Their exchange of 
information and their interactions with Ameri- 
can colleagues related to problems of the bio- 
chemical pharmacology of anticancer agents, the 
design and development of potentially useful 
anticancer compounds, and the preclinical 
testing of such agents for their toxicity and 
efficacy in animal tumor systems. 

Meetings of American-Soviet working groups 
in the program areas of carcinogenesis and can- 
cer prevention will be convened in Moscow in 
early 1983. Prime consideration will be given to 
developing work plans for research activities of 
mutual interest and benefit to cancer patients in 
both nations. 

The spectrum of cooperative cancer research 
activities, under bilateral agreements between 
the NCI and cancer institutes of nine nations, is 
illustrated in Table ^-l. 

Table ^--2 indicates that a total of 236 scien- 
tists~96 from the United States and IkO from 
nine foreign nations— participated in collabo- 
rative cancer research activities under the aus- 



pices of bilateral agreements. More than a third 
of the total number of scientists spent their 
sojourns away from home engaging in one-on- 
one, scientist-to-scientist interactions for col- 
laborative research. Almost a third of the total 
scientist exchangees pursued activities related 
to cancer treatment, drug design and develop- 
ment, and preclinical evaluation of potentially 
useful drugs. Pathology, early detection and 
diagnosis, biochemistry and molecular biology, 
and epidemiology followed as scientific areas of 
high interest and relevance. 



International Cancer Research Data Bank Program 



Established by the National Cancer Act of 
1971, the International Cancer Research Data 
Bank (ICRDB) Program has developed into an 
effective, multifaceted system for the rapid 
exchange of results from cancer research by the 
international team of scientists and clinicians. 
This comprehensive, international resource for 
cancer information provides a unique service to 
cancer researchers almost everywhere in the 
world. To facilitate the transfer of available 



Table 'J- 1.— Cooperative cancer research under bilateral agreements 



Cancer 
research area 



F.R. 
China Egypt France Germany Hungary Italy 3apan Poland U.S.S.R. 



Treatment 

Drug development 
and testing 

Immunology 

Virology 

Genetics 

Epidemiology 

Control and 
education 

Diagnosis and 
detection 

Pathomorphology 

Autocytology 

Carcinogenesis 

Prevention 

Biochemistry 

Radiation biology 



N 


N 


E 


E 


T 


E 


N 


E 
E 


E 


E 
E 


T 


E 

E 
E 




N 


E 


E 


T 


E 



E = in effect 



N = in negotiation 



T = information exchanges and training 
35 



cancer research data, the ICRDB Program has: 
(1) established three online computer data bases 
constituting the CANCERLINE System, which 
enables scientists to retrieve cancer information 
easily at more than 3,000 locations within the 
United States and in 13 other countries; (2) de- 
veloped a series of publications providing com- 
plete coverage of cancer research information, 
in special formats designed for easy use and 
quick reference; and (3) supported a variety of 
specialized information collection, analysis, and 
dissemination activities. 

The Computer Databases of the 
CANCERLINE System 

The three data bases constituting the CAN- 
CERLINE System are CANCERLIT (cancer lit- 
erature), CANCERPR03 (cancer research proj- 
ects), and CLINPROT (clinical protocols). 

CANCERLIT contains nearly 325,000 sub- 
stantive abstracts of information accumulated 
from published scientific papers and from those 
presented at meetings, symposia, and confer- 
ences; books; technical reports; and research 
theses. CANCERLIT is growing at an annual rate 
of nearly ^5,000 abstracts, selected from over 
2,000 biomedical journals. Because of stringent 



input processing requirements and monthly up- 
dating of the CANCERLIT data base, the most 
recently published research results are quickly 
available to cancer researchers worldwide. Since 
early 1980, all new literature entries have been 
indexed with the Medical Subject Heading vo- 
cabulary developed by the National Library of 
Medicine, making retrieval easier during online 
searching. Ten percent of the accessing of CAN- 
CERLIT is conducted by foreign scientists and 
institutions. Activities related to screening, 
indexing, and abstracting cancer-related liter- 
ature are performed for the ICRDB Program 
under contract. 

Descriptions of some 20,000 current cancer 
research projects in 83 countries are the ele- 
ments of the CANCERPROa data base, the most 
comprehensive source available for ongoing 
cancer project information. Included in this data 
base are some 5,000 foreign project descriptions 
collected by an international network of data 
input coordinators. Collection, input, and quar- 
terly updating of the project descriptions in 
CANCERPROJ are performed by a contractor- 
operated Current Cancer Research Project 
Analysis Center. The CANCERPR03 connect 
hours by user type for the first half of FY 1982 
were 216.39. 



Table 'f-2.~The exchange of scientists under NCI's bilateral agreements programs 



Area of specialty 



Collaborating 


Number scientists 
to . . . 


00 
Number scientists E ^ 
from ... " g 

For Individual g §• 
meetings exchanges £ "^ 

ij Q 


Detection <5c 
Diagnosis 


V 

c 

00 

1 

u 
U 


Biochemistry & 
Molecular Biology 


c 
o 

'^ 

u 
■♦-> 
3 

z 


c 
_o 

c 
> 

a 


00 

o 

!2 
£ 
•o 
■q. 




country 


For Individual 
meetings exchanges 


00 

o 
a, 



China 






7 


2 


5 


3 


3 




3 1 




k 




Egypt 










1 












1 




France 




15 


5 


3 


8 


16 


1 


5 


8 




1 




Germany 


(F.R.) 


l4 






2 


^ 


1 








I 




Hungary 




3 


3 




5 


k 


1 




3 






3 


Italy 




5 


7 


20 


7 


27 




1 






11 




Japan 




37 


6 


63 


13 


17 


27 


10 


13 


5 


9 


38 


Poland 






1 




7 


2 




1 


It 


1 






U.S.S.R. 






3 




k 


6 




1 










Totals 




en- 


32 


88 


52 


79 


33 


18 


31 1 


6 


27 


^1 



36 



Summaries of nearly 3,500 experimental can- 
cer therapy protocols are the substance of 
CLINPROT, the data base providing worldwide 
access to information on new procedures, agents, 
and combinations of modalities/agents under 
evaluation for treating cancer patients in major 
American and foreign cancer centers. Of these 
protocols, 1,500 are clinically active while the 
remainder serve as a unique reference source. 
Collection and input of protocol summaries and 
quarterly updating of CLINPROT are functions 
performed by domestic and international con- 
tractors. The connect hours for CLINPROT 
during the first half of FY 1982 were 1^9.03. 

The information contained in the data bases of 
CANCERLINE is available through the compu- 
terized biomedical information network of the 
National Library of Medicine. 

Special Information Activities of 
the ICRDB Program 

Under contracts with the NCI, three Cancer 
Information Dissemination and Analysis Centers 
(CIDAC's) function as information resources in 
three broad areas of cancer research: the CIDAC 
for Diagnosis and Therapy, University of Texas 
System Cancer Center, and M.D. Anderson Hos- 
pital and Tumor Institute, Houston; and the 
CIDAC for Carcinogenesis and for Cancer Vi- 
rology, Immunology, and Biology, both at the 
Franklin Research Center, Philadelphia. Each 
CIDAC is staffed by scientists and served by a 
consultant network with special expertise ap- 
propriate to the fields pertinent to each CIDAC. 
Within its own subject area, each CIDAC pre- 
pares Cancergrams and Oncology Overviews , 
performs custom CANCERLINE searches, and 
provides scientific guidance to the ICRDB 
Program. 

The Clearinghouse for Ongoing Research in 
Cancer Epidemiology is a cooperative project 
sponsored jointly by the ICRDB Program, lARC 
in Lyon, France, and the German Cancer Re- 
search Center in Heidelberg. The clearinghouse, 
located in Lyon, collects, processes, and dis- 
seminates detailed data on research related to 
cancer epidemiology and studies of human can- 
cer causation in countries throughout the world. 
The clearinghouse also prepares lists of epide- 
miology researchers and resources, responds to 
technical inquiries, and produces an annual 
Directory of Ongoing Research in Cancer 
Epidemiology . 

The Latin American Cancer Research Infor- 
mation Project (LACRIP) was developed through 
the ICRDB Program in collaboration with the 
PAHO and its Regional Library of Medicine in 
Sao Paulo, Brazil. LACRIP serves as the source 
for identifying, collecting, and supplying Latin 
American biomedical literature, summaries of 
ongoing cancer-related research projects, and 
active therapy protocols in Latin America for 



inclusion in the CANCERLINE system. PAHO 
also serves as the center for searching ICRDB 
data bases and providing documents and data in 
response to requests for information from cancer 
researchers in Latin America. In addition, an 
automatic service that selectively disseminates 
information to cancer researchers and clinicians 
in Latin America is provided. 

Through LACRIP, a series of collaborative 
cancer treatment research projects was devel- 
oped between 10 cancer centers in the United 
States and 12 cancer centers in Latin America. 
Although these activities are now supported 
completely by the NCI Division of Cancer Treat- 
ment, LACRIP maintains the clinical data 
gathered at the Latin American centers. 
LACRIP also arranges for the exchange of pro- 
fessional staff between the American and the 
Latin American centers to promote a better 
understanding of current cancer treatment 
research and modalities of therapy available in 
the United States. 

In cooperation with the International Union 
Against Cancer, the ICRDB Program provides 
partial support for a special Committee for 
International Collaborative Activities (CICA) 
within the framework of the union. One of the 
CICA activities is the collection of data on 
ongoing cancer research projects, including 
clinical protocols, from more than 70 countries. 
CICA personnel identify and promote collabo- 
rative projects among cancer centers and cancer 
scientists in different countries. CICA period- 
ically publishes an updated International Direc - 
tory of Specialized Cancer Research and Treat - 
ment Establishments , which describes more than 
700 of the world's cancer centers, their cancer 
research and treatment activities, and their 
resources. The International Cancer Patient 
Data Exchange System (ICPDES) has been es- 
tablished as part of the CICA project. Currently, 
scientists and clinicians from nine European and 
five American cancer centers participate in this 
study, which could result in the development and 
establishment of the first internationally rec- 
ognized and standardized tumor registr>', from 
which valuable comparative data would be pro- 
vided from a multitude of countries on cancer 
epidemiology, treatment, and prevention. 

Entries of cancer case data for six different 
cancers, from each of the participating centers, 
is detailed in table k-2>. The entries for each 
cancer site were accumulated from November 
1977 through July 1981. 

Scientist-to- Scientist Communication 

The ICRDB Program, through the International 
Union Against Cancer in Geneva, Switzerland, 
encourages international scientist-to-scientist 
communication through the International Cancer 
Research Technology Transfer Program 
(ICRETT). The goal of this program is to 



37 



Table 'f-S.— Patient data, by cancer site and collaborating institute, 
entered into the ICPDES system 





Breast 


Colon 


Rectum 


Larynx 


Hodgkin's 


Non-Hodgkin's 


Total 


M.D. Anderson 


3,119 


1,055 


548 


383 


384 


„ 


5,489 


Mayo 


1,370 


922 


508 


201 


181 


268 


3,450 


Memorial 


3k7 


178 


177 


70 


55 


~ 


1,427 


Roswell Park 


375 


204 


106 


50 


49 


38 


822 


Duke 


121 


31 


30 


15 


16 


1 


214 


Total U.S. 


5,932 


2,390 


1,369 


719 


685 


307 


11,402 


Amsterdam 


619 


28 


99 


32 


57 


95 


930 


Essen 


236 


12 


14 


8 


36 


65 


371 


Heidelberg 


272 


61 


26 


5 


36 


84 


484 


Milan 


1,47^ 


106 


119 


184 


118 


~ 


2,001 


Moscow 


818 


58 


151 


126 


153 


— 


1,306 


Rotterdam 


1,519 


74 


167 


224 


110 


95 


2,189 


Bordeaux 


1,149 


82 


159 


149 


140 


49 


1,728 


Brussels 


674 


13 


73 


93 


37 


13 


903 


Budapest 


1,563 


48 


98 


239 


127 


5 


2,080 


Total Europe 


8,324 


482 


906 


1,060 


814 


406 


11,992 


Total ICPDES 


14,256 


2,872 


2,275 


1,779 


1,499 


713 


23,394 



promote direct and rapid transfer of information 
about new or improved technology or methodol- 
ogy between two or more investigators, located 
in different countries, working on similar re- 
search projects. This interaction is accomplished 
by the support of short-term visits to conduct 
collaborative research projects in a short time, 
usually 2 to 4 weeks. Since the inception of the 
program in 1975, 586 awards had been granted 
through 3uly 1982. 

In many instances, these associations between 
scientists from different countries developed 
into significant collaborative studies that other- 
wise might have lacked the necessary impetus 
and resources to develop. For instance, a 
geneticist from the Department of Tumor Biol- 
ogy of the Karolinska Institutet in Stockholm is 
pursuing molecular analyses of chromosomal 
translocations in cancer. Through the literature, 
he learned of a scientist at the Beatson Institute 
for Cancer Research in Glasgow, Scotland, who 
has sorted out specific chromosomes and iden- 
tified their molecular breakpoints. These break- 
points led to chromosome translocations asso- 
ciated with chronic granulocytic leukemia and 
Burkitt's lymphoma. Newly developed techniques 
for chromosome sorting by means of the fluor- 
escence activated cell sorter (FACS) were used. 
Although the Swede had a new FACS available to 



him in his own institute, he had had difficulty in 
applying the instrument for the analyses he 
wished to perform. During a 3-week exchange, 
he was able to learn about the features of this 
unique apparatus and apply FACS techniques for 
chromosome sorting as well as cloning proce- 
dures for small amounts of DNA from trans- 
located chromosomes. Overall, communication 
between the two scientists supported their col- 
laborative research. 

A biochemist from the Institute of Molecular 
Biology in Salzburg, Austria, spent 1 month in 
the laboratory of a fellow biochemist at Wash- 
ington University, St. Louis, Missouri. Both were 
working on collagenase production in human and 
animal tumors, recognizing that several human 
and animal carcinomas contain collagenase and 
release this enzyme in vitro. They perceived, as 
well, that the role of collagenase in growth and 
invasiveness of tumor has not been explained 
precisely. The Austrian was interested in a more 
sensitive method to detect small amounts of 
collagenase in the supernatant fluid of tumor 
cells. He learned of the American biochemist's 
modification of the enzyme-linked immunosor- 
bent assay, which he believed would meet his 
own requirements. During his sojourn with the 
American biochemist, the Austrian scientist was 
able to master the new technique and return to 



38 



his laboratory where he is now studying the de 
novo synthesis of coUagenase, the nature of the 
latent enzyme, and the source of this enzyme in 
human skin carcinoma. The successful collabo- 
rative efforts of the two biochemists continue. 

A biochemical pathologist from the Yale Uni- 
versity School of Medicine had been studying the 
phenomenon of epidermal (epithelial) cell move- 
ment, which is relevant to the histologic and 
pathologic process of wound closure and epi- 
thelial cancer cell invasion and metastasis. In 
analyzing these processes, he isolated a molecule 
from serum that epithelial cells need in order to 
move in vitro . This molecule, a glycoprotein 
named epibolin, is necessary and sufficient for 
epidermal cell movement. In the absence of 
serum, no epidermal cell spreading is observed, 
and in the presence of epibolin-antibody, serum 
does not support epidermal cell spreading. The 
purpose of his visit with a colleague at the Uni- 
versity of Zurich was to learn what specific role 
the spreading protein plays in the movement of 
cancer cells, since cancer cell motility is central 
to the problem of neoplastic invasion and metas- 
tasis. The Swiss scientist, a world-renowned 
scholar of cancer cell movement, developed 
unique methods for measuring cancer cell mo- 
tility. In addition, he developed several squamous 
cell carcinoma lines for such studies. By virtue 
of his experience in Switzerland, the American 
scientist was able to confirm his hypothesis and 
his experiments are consonant with the con- 
clusion that the glycoprotein epibolin is the 
necessary component for in vitro spreading of 
cells from human squamous carcinoma. 

A radiotherapist/epidemiologist from the John 
F. Kennedy Memorial Hospital in Monrovia, 
Liberia, journeyed to the NCI of Canada, in 
Toronto, where he spent 1 month designing, 
constructing, administering, and analyzing 
questionnaires for case-control and cohort 
studies used in epidemiology. After learning 
about questionnaire design, questionnaire meth- 
ods, and indepth interviewing, he attended field 
studies with several Canadian interviewers to 
gain practical insight into problems associated 
with interviewing. He learned the procedures for 
choosing controls for the various types of case- 
control and cohort studies as well as the vali- 
dation and sensitivity of testing and final eval- 
uation of data. At the end of his stay, he was 
able to put together the skeleton of a question- 
naire for a case-control study scheduled for 
completion in Liberia and tried out first in a 
pilot study and later as a multicenter study in 
collaboration with his colleagues in Africa. 

A surgeon from the Yale University School of 
Medicine pursued intense study for 3 weeks with 
a surgeon from the University Hospital in Zurich, 
from whom he obtained instruction in both sur- 
gical anatomy of the cranial base and the actual 
operative technique for treatment of tumors 
located at the skull base. The principal deter- 



minant of patient survival in the treatment of 
tumors in this anatomical site involves the abil- 
ity to obtain total gross tumor removal before 
instituting adjuvant radio- or chemotherapy. 
Through actual observation of surgical proce- 
dures, video tapes, and the use of the Swiss 
surgeon's extensive library, the American sur- 
geon obtained a good deal of firsthand, practical 
information. This experience enabled him to 
perform the Swiss procedure at Yale. 

A photochemist from the Agricultural Re- 
search Organization in Bet Dagn, Israel, spent 1 
month in the Laboratory of Pathophysiology of 
the NCI. He wanted to understand the initial 
chemical events that follow photoexcitation of 
the porphyrin molecule and its subsequent inter- 
action with other cell constituents. He was in- 
terested in optimizing data for the preferential 
uptake and retention by malignant tumors of 
porphyrins, which are photochemically active 
compounds. Because porphyrins are efficient 
photodynamic sensitizers and certain malignant 
cells become fully vulnerable to light, he hoped 
to learn the mechanism(s) by which tumor cells 
are inactivated during exposure to porphyrin and 
irradiation. 

An English biochemist/physician spent 2 weeks 
in the Cancer Treatment and Research Center in 
San Antonio, Texas, to study the techniques 
currently used to grow colonies of human tumor 
cells on soft agar. The visit and exchanges en- 
abled him to make small but important modifi- 
cations to the techniques currently used in his 
laboratory for the culture of ovarian, breast, and 
colonic carcinoma. As well, he was able to com- 
pare the up-to-date results obtained from cyto- 
toxic drug assays in this laboratory using reduc- 
tion in colony-forming activity as an end point. 
Since his return to South Hampton, England, he 
has been able to redefine the objectives of his 
present project towards: (1) using an animal 
model to see if the in vitro assay can be truly 
predictive of in vivo activity of cytotoxic drugs; 
and (2) looking more closely at the biology of 
colony formation by tumors and to improve the 
proportion of growing in vitro. 

In summary, table ^-^^ designates the disci- 
plinary studies pursued by the 586 ICRETT 
awardees, while table ^-5 indicates the inter- 
national flavor of the ICRETT Program and the 
interaction between scientists from ^7 coun- 
tries/areas. 

NIH Visiting Program 

During 1982, scientists of the NCI received 
260 Visiting Scientists, Associates, and Fellows 
from ^5 countries who came to the United States 
to engage in collaborative cancer research 
activities. Five of the visitors were appointed as 
Experts and 68 came as Guest Workers, whose 
financial support was provided by sources other 



39 



Table '^-'^.--International cancer research technology transfer 



Disciplines 



1976 1980 1981 1982 

6 1977 1978 1979 + Apr 81- April/ Total 

months 3FM 81 Mar 82 June 



Epidemiology, biostatistics, and registries 


— 


3 


5 


7 


7 


5 


2 


29 


Biochemistry, molecular biology, and 
biophysics 


5 


l^f 


l^t 


11 


11 


7 


2 


6'f 


Viral carcinogenesis 


7 


13 


10 


9 


11 


6 


1 


57 


Chemical carcinogenesis 


3 


U 


8 


13 


12 


5 


1 


56 


Cell biology and cell genetics 


1 


15 


11 


8 


19 


I'f 


2 


70 


Experimental pathology 
(including histopathology and cytology) 


It 


5 


12 


1^^ 


10 


3 


1 


«^9 


Immunology 


5 


19 


25 


31 


33 


11 


— 


I2tt 


Experimental chemotherapy 


6 


3 


2 


9 


2 


2 


~ 


2k 


Surgery 


~ 


1 


2 


~ 


tt 


~ 


1 


8 


Clinical chemotherapy and endocrinology 


2 


3 


1 


8 


7 


3 


— 


2k 


Radiobiology and radiotherapy 


5 


t* 


7 


10 


9 


7 


1 


k3 


Controlled therapeutic trials 


1 


— 


1 


1* 


~ 


— 


~ 


6 


Detection and diagnosis 


1 


6 


'f 


1 


8 


1 


— 


21 


Behavioral and social sciences and the 










-^--- 








relationship to cancer 


.-- 


— 


1 


~ 


11- 


1 


~ 


6 


Environmental factors and prevention 


— 


2 


~ 


1 


2 


~ 


— 


5 


Totals 


W 


102 


103 


126 


139 


65 


11 


586 



than the NCI. These visiting scientists pursued 
their research in the laboratories of the NCI 
Divisions of Cancer Treatment, Cancer Cause 
and Prevention, and Cancer Biology and Diag- 
nosis. These mutually beneficial associations 
afforded the NCI host scientists opportunities to 
learn from their visitors about cancer problems 
in a given foreign country; about factors peculiar 
to that nation that might be related to the mor- 
bidity and mortality of cancer; and about activ- 
ities underway toward the management, treat- 
ment, and prevention of cancer. Reciprocally, 
the foreign visitors enjoyed unique opportunities 
to improve their mastery of the scientific meth- 
od or to develop their potential for significant 
contributions to basic and /or clinical research. 
The value of this scientific interaction is indis- 



putable because cancer patients throughout the 
world are benefiting from improved care. 

Extramural Programs 

During 1982, the Divisions of Cancer Treat- 
ment (DCT) and Cancer Cause and Prevention 
(DCCP) maintained extensions of their program- 
matic objectives in foreign countries through 18 
contract research activities, compared to 3k 
during the previous year and 53 during 1980. No 
contractual research was in effect to extend the 
research effort of the Division of Cancer Biology 
and Diagnosis (DCBD). 

The Division of Extramural Activities (DEA) 
provided the fiscal support, through 59 grants, to 



kO 



scientists in foreign institutions conducting basic 
and applied cancer research. 

Institutions in 17 nations were recipients of 
NCI grants and contracts. Thus, the outreach of 
NCI support extended to Australia, Belgium, 
Canada, Denmark, Finland, France, Ghana, 
Israel, Italy, Japan, Korea, South Africa, Swe- 
den, Switzerland, Tanzania, Tunisia, and the 
United Kingdom. 

Division of Cancer Treatment 

DCT research contracts have been awarded to 
investigators in nine institutions of five foreign 
countries for studies related to the characteri- 
zation of anticancer agents, the search for po- 
tentially useful anticancer agents such as those 
of microbial and natural origin, the screening 
and testing of such compounds, their biochemical 
pharmacology and toxicology, the synthesis of 
radiation sensitizing agents, and clinical trials on 
specific cancers. One contract is specifically for 
the production and delivery of human lympho- 
blast interferon. Examples follow of this inter- 
national collaborative effort in cancer drug 
design and development and in preclinical and 
clinical evaluation. 

Through its Cancer Chemotherapy Research 
Collaborative Office at the Institut Jules Bordet 
in Brussels, Belgium, the DCT maintains inter- 
action with investigators of European nations 
concerning ongoing cancer research programs on 
both continents. The Brussels office has been 
especially useful in disseminating information on 
experimental and clinical pharmacology and 
clinical trials and organizing symposia conducted 
jointly by American and European investigators. 
The Institut Jules Bordet provides a flow of new 
agents with potential anticancer activity to the 
European pharmaceutical industry. 

Under contract, materials collected in nor- 
thern Europe are screened against animal tumors 
at the Institut Jules Bordet in accordance with 
established in vivo protocols. Approximately 
11,000 substances that have been identified as 
potentially useful anticancer agents are cur- 
rently being tested. 

Under contract to the NCI, the Institute of 
Cancer Research in England is conducting re- 
search on design, synthesis, and evaluation of 
novel compounds, both nitroimidazoles and other 
heterocycles, as potential radiation sensitizers. 
Several classes of heterocycles have been syn- 
thesized and are in the process of evaluation. 
Other activities in the Institute of Cancer Re- 
search involve: (1) validation of human tumor 
xenografts as models for cancer chemotherapy; 
(2) the use of human tumor xenografts and 
transplantable mouse tumors for testing new 
compounds of interest to the NCI; (3) the toxi- 
cology, pharmacology, and initial clinical trials 
of new drugs developed in this project; and W 
studies of the biochemical basis for treatment 



Table 'f-^.—Countries/areas of origin of 

ICRETT awardees and their destinations, 

1976-82 



Origin 




Destination 




Argentina 


15 


Argentina 


1 


Australia 


^ 


Australia 


10 


Austria 


6 


Austria 


1 


Belgium 


9 


Belgium 


6 


Brazil 


6 


Canada 


12 


Bulgaria 


3 


P.R.C. 


8 


Canada 


15 


Taiwan 


1 


P.R.C. 


7 


Colombia 


1 


Taiwan 


2 


Denmark 


5 


Colombia 


1 


Finland 


7 


Czechoslovakia 


3 


France 


35 


Denmark 


1 


Germany (F.R.) 


35 


Egypt 


1 


Hungary 


2 


Finland 


5 


Iceland 


1 


France 


37 


India 


2 


Germany (F.R.) 


27 


Israel 


8 


Greece 


if- 


Italy 


10 


Hungary 


1+ 


Japan 


Ik 


India 


18 


Malaysia 


1 


Iran 


2 


Mexico 


1 


Israel 


l^6 


Netherlands 


11 


Italy 


k2 


New Zealand 


3 


Japan 


15 


Norway 


k 


Kenya 


1 


Peru 


1 


Liberia 


2 


Poland 


I 


Malaysia 


2 


Sweden 


3k 


Mexico 


3 


Switzerland 


29 


Netherlands 


11 


United Kingdom 


69 


New Zealand 


2 


U.S.A. 


258 


Nigeria 


8 


U.S.S.R. 


3 


Norway 


12 


Venezuela 


2 


Peru 


1 
1 






Philippines 






Poland 


11 


31 countries/areas 


586 


South Africa 


1 






Spain 


^ 






Sri Lanka 


2 






Sweden 


2^ 






Switzerland 


5 






Thailand 


3 






Turkey 


1 






Uganda 


1 






United Kingdom 


7k 






Uruguay 


2 






U.S.A. 


135 






Yugoslavia 


6 






Zambia 


1 






1^7 countries/areas 


586 





k\ 



Table tt-G.—The NCI-PAHO collaborative cancer treatment research program 
by number of protocols and patient accrual 



Latin American Center 



Protocols USA Cancer Center 



Patient 
accrual 



Grupo Argentine de Tratamiento 

de Ids Tumores Solidos (GATTS) 
Buenos Aires, ARGENTINA 

Grupo Argentine de Tratamiento 

de la Leucemia Agunda (GATLA) 
Buenos Aires, ARGENTINA 

Institute Angel H. Roffo 
Buenos Aires, ARGENTINA 

Institute Nacienal de Cancer 
Rio de Janeiro, BRAZIL 



Fundacae A.C. Camarge 
Sao Paulo, BRAZIL 



Universidad Catelica de Chile 
Santiago, CHILE 

Institute Nacienal de Cancerologia 
Bogota, COLOMBIA 

Hospital de Nines "Dr. C.S. Herrera" 
San 3ese, COSTA RICA 

Hospital San Juan de Dies 
San Jose, COSTA RICA 

Hospital de Oncolegia 
Mexico City, MEXICO 

Institute Nacienal 

de Enfermedades Neeplasicas 
Lima, PERU 

Hospital de Clinicas 

"Dr. Manuel Quintela" 
Montevideo, URUGUAY 

Institute de Oncolegia "Luis Razetti" 
Caracas, VENEZUELA 

13 centers/9 countries 



NA 



NA 



NA 



26 



Georgetown University 168 

Washington, D.C 



Georgetown University 3^1 

Washington, D.C. 



Georgetown University 15 

Washington, D.C. 

M.D. Andersen Hospital 137 

and Tumor Institute 
Houston, TEXAS 

Memorial Sloan-Kettering ^^5 

Cancer Center 
New York, NEW YORK 

Wisconsin Clinical Cancer Center IJ^t 

Madison, WISCONSIN 

Roswell Park Memorial Institute 98 

Buffalo, NEW YORK 

Baylor University Medical Center (NA) 

Dallas, TEXAS 

Baylor University Medical Center (NA) 

Dallas, TEXAS 

New York University Cancer Center it5 

New York, NEW YORK 

Comprehensive Cancer Center 608 

for the State of Florida 
Miami, FLORIDA 

University of Maryland 109 

Cancer Center 
Baltimore, MARYLAND 

Yale University Medical Center (NA) 

New Haven, CONNECTICUT 

10 centers IS'fO 



NA = newly admitted to CCTRP. 



^2 



response or failure aimed at the design, syn- 
thesis, and detailed evaluation of new drugs. 

Under contract, the NCI maintains a Chemo- 
therapy Liaison Office in the Japanese Founda- 
tion for Cancer Research in Tokyo. The program 
is designed to foster close collaboration between 
American and Japanese investigators in the 
development and application of new clinical 
anticancer drugs and in the exchange of pre- 
clinical experimental and clinical scientific 
knowledge and materials requisite for maximum 
progress in cancer therapy. 

Scientists at the Mario Negri Institute of 
Pharmacologic Research in Milan, Italy, aid the 
NCI, under contract, with a multidisciplinary 
approach to drug development. The research 
tasks include: (I) collection and screening of 
antineoplastic agents obtained from southern 
Europe; (2) screening of immunochemotherapeu- 
tic agents; and (3) pharmacologic studies of new 
agents with emphasis on the relationship of 
pharmacokinetics with in vivo antitumor effects. 

In association with the Muhimbili Medical 
Center in Tanzania, the OCT is engaged in a 
study of the use of oral 1 3-cis retinoic acid as a 
chemopreventive agent of skin cancer in albino 
Africans. These people, living in the equatorial 
zone, are subject to the most intense ultraviolet 
radiation on the surface of the earth and there- 
fore to a 100 percent greater probability of skin 
cancer. 

Five years ago, through the ICRDB Program's 
special information activity, LACRIP, collabo- 
rative clinical studies were developed among 
nine cancer centers in the United States and six 
centers in Latin America. This cooperative re- 
lationship with Latin American cancer institutes 
is now managed by the DCT as the NCI-PAHO 
Collaborative Cancer Treatment Research Pro- 
gram. Currently, investigators in 13 Latin Amer- 
ican cancer institutes/hospitals and in 10 Amer- 
ican cancer centers are pursuing joint research 
activities. The treatment protocols now in eval- 
uation include therapeutic concepts in hemato- 
logic malignancies, childhood malignancies, 
breast cancer, gynecologic cancer, gastroin- 
testinal cancer, and osteosarcomas. Multimodal 
concepts in solid tumors are being pursued in 
advanced breast and head and neck cancer. Over 
the total life of the program as many as 37 
therapy protocols have been active in a given 
year. Eleven of these protocols have been com- 
pleted or terminated, leaving 26 still under ac- 
tive investigation. Since the inception of this 
multinational effort, 2,3^^2 patients have been 
accrued under the various protocols. The col- 
laborating cancer centers, the numbers of active 
protocols, and patient accrual are listed in table 
^-6. Table 't-Z indicates the cancers being stud- 
ied in various organ sites. 

Personnel of the DCT play key roles in the 
NCI bilateral agreements with China, Egypt, 
France, the Federal Republic of Germany, Italy, 



Japan, and the U.S.S.R. through participation in 
clinical trials, preclinical screening and testing 
of potentially useful anticancer agents, evalua- 
tion of the activity of substances indicating 
properties for biologic response modification, 
and programs in experimental/development 
therapeutics. 

Division of Cancer Cause and Prevention 

The DCCP maintains active associations with 
international organizations and agencies that 
have well-defined objectives in cancer research, 
especially its cause and prevention. The DCCP is 
also engaged in collaborative contract research 
in seven institutions or agencies in six foreign 
nations. These foreign extensions of the DCCP 
research program enable the Division to support 
fundamental studies on normal and malignant 
cells in relation to such carcinogens as viruses 
and chemicals, as well as epidemiologic studies 
of human populations for the identification of 
risk factors predisposing individuals to various 
cancers. Excellent model systems are available 
to scientists studying the effects of potentially 
carcinogenic factors in the environment. Thus, 
studies are related primarily to three major 
program areas within the DCCP: biologic car- 
cinogenesis, chemical/physical carcinogenesis, 
and epidemiology. 

The binational programs on which the DCCP 
collaborates provide significant epidemiologic 
opportunities for cancer research. This year, 
joint studies and exchange programs enabled 
scientists of the Cancer Institute Hospital in 
Beijing to pursue clues drawn from the recent 
county-based maps in China and to study the 
changing risks among Chinese migrants to the 
United States. Reports were prepared on the 
geographic correlations within China between 
cancers of the cervix and penis and colorectal 
cancer and schistosomiasis and on the patterns 
of childhood cancer in Chinese populations 
around the world. Collaborative analytic inves- 
tigations on cancers of the esophagus and lung, 
trophoblastic neoplasms, and T cell leukemia are 
also being developed. 

Through a contract with the DCCP, scientists 
at the Chaim-Sheba Medical Center in Israel are 
determining the incidence of cancer in 10,000 
Israeli children irradiated for ringworm of the 
scalp, in 10,000 nonexposed persons selected 
from the general population, and in 5,000 non- 
exposed siblings. This effort is of significance in 
the study of patients irradiated for benign dis- 
eases because it allows an evaluation of biologic 
mechanisms for carcinogenesis in humans. The 
minimal confounding effects of carcinogenic 
influences, and the possibly greater suscepti- 
bility of young people to environmental carcin- 
ogens, improve the chances of detecting radio- 
genic effects and provide an opportunity for 
lifetime studies of cancer incidence. 



1^3 



Table 'J-7.--NCI-PAHO collaborative cancer treatment research program 
by location and number of active protocols 



Active protocols 













m 




















(A 


E 
o 

•4-> 






■<3 

C 


1 n) 


u 




0) 


c 

■o 

c 
m 

■V 
n) 


00 

c 


O 

E 

3 
C 

'3 


W3 

o 

■D 


£ 
o 


IS 

E 
o 
u 


i) 
+-• 

c 

o 

■!-• 




1 
"o 

c 


PAHO nation and center 




a; 

I 


3 






s 


(a 


a 


>% 
J 




Argentina GATTS ^ 














1 


1 






GATLA ^ 








1 


1 




1 




2 




ROFFO 




1 
















1 


Brazil Rio de Janeiro 




1 


















Sao Paulo 




1 


















Chile 


1 














1 






Colombia 


















1 




Mexico 




















1 


Peru 


3 


1 










1 


1 




2 


Uruguay 




1 


1 






1 










Total 


t^ 


5 


1 


1 


1 


1 


3 


3 


3 


if 



Total 



2 
5 
2 
1 
1 
2 
1 
1 
8 
3 
26 



^ Grupo Argentino de Tratamiento de los Tumores Solidos - Hospital Militar Central 
° Grupo Argentino de Tratamiento de la Leucemia Aguda 



Division of Extramural Activities 

Grants by the DEA have been made available 
to institutions and organizations in 1 1 foreign 
countries. The scientific investigations under the 
59 DEA grants include both basic and applied 
research and range across the spectrum of the 
thrusts and objectives of the NCI. Among these 
are the National Research Council of Canada's 
assays for and studies of the action of carcino- 
gens and "promoters" of carcinogenesis. Other 
studies being pursued in Canadian universities 
and institutions include the pathogenesis of liver 
cancer induced by chemicals, the role of anti- 
tumor action of nitrosoureas, DNA repair/ 
replication in chemical carcinogenesis, the me- 
tabolism and carcinogenicity of haloaromatic 
pollutants, and melphalan interaction with amino 
acids in human cells. At the University of Lon- 



don a study is underway on the metabolic ac- 
tivation of the polycyclic hydrocarbons as well 
as a study of the therapeutic response of human 
tumor xenografts. In Finland, at the University 
of Helsinki, investigations are being pursued of 
natural and tissue-specific immunity to human 
neoplasms and fibronectin and its loss in malig- 
nant transformation. Scientists at the Weizmann 
Institute of Science in Israel are studying the 
control of gene expression in tumor viruses and 
in cells. At that institution, as well, studies are 
underway of receptors and growth factors for 
neoplastic cells and the modulation of cellular 
responses by membrane fluidity. 

These research grant activities provide the 
NCI with opportunities to associate with and 
take advantage of the foreign expertise available 
in basic and clinical research that is directly 
relevant to the thrusts and goals of the NCI. 



^^ 



Chapter V 



National Heart, Lung, and Blood Institute 



Introduction 



The United States plays an important role in 
international efforts to control heart, lung, and 
blood diseases. This role has evolved through the 
contributions of the U.S. scientific community, 
in concert with the U.S. national programs ini- 
tiated under the 1972 mandate from the Presi- 
dent and the Congress. The mandate, while sig- 
nificantly broadening the scope and depth of the 
programs of the National Heart, Lung, and Blood 
Institute (NHLBI), also created new opportunities 
for U.S. scientists to collaborate with scientists 
engaged in similar efforts in other countries. The 
concerted government and private sector efforts 
implemented in the United States in recent years 
have resulted in significant improvements in the 
health of the U.S. population. While mortality 
rates for coronary heart disease are increasing in 
many countries, they have been declining in the 
United States. In recognition of this success, the 
international medical research community hopes 
to learn important lessons from the U.S. national 
programs. Thus, scientists and administrators in 
other countries frequently look to the United 
States for expertise in research methodology, 
design strategies, and implementation of re- 
search findings at the community level. Con- 
versely, through the Institute's international 
programs, U.S. scientists are able to carry out 
comparative studies and analyses not possible 
through national efforts alone. A number of 
bilateral agreements have been drawn up that 
combine U.S. resources with those from other 
countries on a cost-sharing basis. 

The broad goals of the NHLBI international 
programs are 

• To develop international programs relevant 
to the goals and priorities of the U.S. na- 
tional programs in heart, lung, and blood 
diseases and blood resources; and 

• To develop international contacts, activi- 
ties, and programs of mutual interest and 
benefit to the United States and to the 
cooperating country or countries in areas 
related to the Institute's national mission. 

The NHLBI international programs emphasize 
basic research to enhance data generated in 



domestic studies, clinical investigations, design 
and implementation of epidemiological studies, 
and programs in prevention, education, and con- 
trol. By combining international resources with 
national resources, scientists can use scarce 
research funds more effectively in the United 
States as well as in the collaborating countries. 
Joint studies by U.S. and foreign scientists with 
complementary skills, approaches, or resources 
accelerate scientific research by consolidating 
the management of the research problem, en- 
suring comparability of data, and generally im- 
proving the analysis of data. 

NHLBI international programs have impacts on 
health problems in the United States and abroad. 
A growing network of countries is interested in 
studies similar to those implemented by the 
NHLBI. The Lipid Research Clinics studies are 
an example of the strong international effort in 
arteriosclerosis. Under NHLBI sponsorship, epi- 
demiological data have been collected since 
1972-73 on populations in the United States, 
Canada, Israel, and the U.S.S.R. Analyses of the 
data and publications of the results are contin- 
uing. These studies compare lifestyles to genetic 
determinants of cardiovascular disease, with 
specific emphasis on the prevalence of lipid 
disorders in different populations. Perhaps the 
most important contribution of these studies is 
the international standardization of data col- 
lection and analyses. These procedures are also 
being used to organize similar studies in China 
and Poland so that future comparisons between 
the United States and these two countries will be 
possible as well. In a similar study sponsored by 
PAHO, clinics in Mexico, Brazil, and Jamaica 
will be standardized to generate comparable 
data on nutrition and cardiovascular diseases in 
Latin America and Caribbean populations. 

Broad international interest in hypertension 
has also been generated. The success of the 
Institute's National High Blood Pressure Educa- 
tion Program (NHBEP) and the Hypertension 
Detection and Followup Program (HDFP) has 
contributed to this interest. For instance, the 
Federal Republic of Germany is using these 
programs as models for its High Blood Pressure 
Education Program initiated in 1980. Activities 
planned under the U.S. -Kuwait Technical Coop- 
eration Program in Health also build on the 
experiences gained in the NHBEP and HDFP. 



^5 



Studies of hypertension are important compo- 
nents of the bilateral programs with China, 
Japan, and the U.S.S.R. Each of these bilateral 
programs provides unique opportunities for ex- 
panding the knowledge base gained from U.S. 
national data. In the case of the U.S. -U.S.S.R. 
program in hypertension, the joint studies em- 
phasize biobehavioral research. The U.S. -Japan 
studies focus on the role of nutrition, while the 
U.S.-P.R.C. cooperation explores the factors 
that may be responsible for the observed dif- 
ferences in rates of hypertension in north and 
south China. 

The above examples show how studies initiated 
by NHLBI have generated interest in other 
countries and international organizations in 
testing similar hypotheses in a multinational 
context. The insights resulting from these anal- 
yses can lead to a broader understanding of the 
relative importance of diet, heredity, lifestyle, 
and environment in the etiology of cardiovas- 
cular disease. These studies may also lead to new 
approaches to the treatment and prevention of 
cardiovascular disease. 

Although NHLBI international activities in 
basic research are conducted on a relatively 
small scale, results can have important impli- 
cations for the broader scientific community. 
Research results from U.S. cooperation with 
Italy, France, Japan, the Federal Republic of 
Germany, and the U.S.S.R. are described in this 
report. 

One important impact of the NHLBI interna- 
tional programs has been on the scientific lit- 
erature. Under the bilateral programs, U.S. 
scientists and foreign experts have collaborated 
on many scientific publications, proceedings, and 
books, making the information available to the 
scientific community at large. These publica- 
tions report on the results of joint planning of 
research, joint implementation, and joint anal- 
yses of data in a manner not possible through 
national approaches alone. A number of proceed- 
ings of U.S.-U.S.S.R. joint symposia were pub- 
lished in FY 1982. Several books, reporting on 
the results of U.S. -Italy joint cooperation, have 
been published by Raven Press and Karger Ver- 
lag. The proceedings of a U.S. -Poland joint sym- 
posium on cardiovascular disease have also been 
published. The first papers from the U.S.-P.R.C. 
studies are being prepared for publication. 

Summary of International Programs 
and Activities 

The Institute's international programs and 
activities are carried out within the Institute's 
mandates under the National Heart, Lung, and 
Blood Program. The following sections summa- 
rize NHLBI cooperative activities with other 
countries during FY 1982. 



Bilateral Agreements and Other 
Country-to-Country Activities 

Canada 

Cardiovascular disease is the leading cause of 
death in Canada, as in the United States. Mor- 
tality from this disease has been declining in 
both countries, although more rapidly in the 
United States than in Canada. U.S. -Canadian 
cooperation in areas related to NHLBI's mission 
has been longstanding. Many NHLBI-sponsored 
clinical trials have a Canadian component. In FY 
1982, Canadian investigators participated in the 
following studies: 

• The Beta Blocker Heart Attack Trial: A 
trial, completed in October 1981, that dem- 
onstrated the effectiveness of the drug 
propranolol in reducing mortality among 
heart attack victims; 

• Coronary Artery Surgery Study: A study to 
evaluate the efficacy of coronary artery 
bypass surgery in reducing morbidity and 
mortality from heart disease; 

• Lipid Research Clinics Program: An in- 
ternational network of clinics conducting 
the Coronary Prevention Trial to test the 
hypothesis that reduction of serum choles- 
terol in men with elevated cholesterol will 
reduce coronary heart disease; 

• Multiple Risk Factor Intervention Trial: A 
prevention program to investigate whether 
modification of three cardiovascular disease 
risk factors—smoking, high blood pressure, 
and elevated serum cholesterol—will reduce 
the incidence of myocardial infarction and 
death from coronary heart disease; 

• Clinical Study of Intermittent Positive 
Pressure Breathing: A trial to evaluate the 
effects of this treatment when used as an 
adjunct to the care of ambulatory patients 
with chronic obstructive lung disease; 

• Prevention of Neonatal Respiratory Dis- 
tress Syndrome with Antenatal Steroid 
Administration: A trial to determine 
whether antenatal administration of steroids 
can reduce the incidence, morbidity, and 
mortality from this condition among infants 
at risk. 

China 

An agreement between the Government of the 
United States and the Government of the Peo- 
ple's Republic of China on Cooperation in Sci- 
ence and Technology was signed in January 1979. 
The subsequent U.S.-P.R.C. Protocol for Coop- 



^6 



eration in Science and Technology of Medicine 
and Public Health, signed in June 1979, identi- 
fied cardiovascular disease as one of the seven 
areas of initial cooperation. 

At the U.S.-P.R.C. Second Joint Science and 
Technology Commission Meeting in October 
1981, the U.S. cochairman noted that the coop- 
erative program ranked with those of highest 
priority to the United States and that the joint 
activities were now yielding mutually beneficial 
results. One such activity has been the develop- 
ment of a joint protocol for collaborative re- 
search on the epidemiology of cardiovascular 
disease and its risk factors. The protocol defines 
a study of urban and rural populations (men and 
women) in north and south China. After comple- 
tion of a pilot study in the spring of 1982, the 
U.S. working group visited China in the fall of 
that year to initiate the laboratory standardi- 
zation program, train staff, prepare study forms, 
and discuss data processing and methodology of 
the biochemical measurements. 

During FY 1982, a number of Chinese dele- 
gations visited the NHLBI. In May 1982, a P.R.C. 
study group on advances in research on athero- 
sclerosis met with Institute staff to discuss 
current research in atherogenesis, hypertension, 
nutrition and cardiovascular disease, pathology, 
and the Lipid Research Clinics Program. Later 
that month the director of the new Beijing 
Heart, Lung, and Blood Vessel Medical Center 
and a member of his staff visited the NHLBI. 
Two Chinese specialists in lung diseases held 
in-depth discussions with the staff of the 
NHLBI's pulmonary laboratories. In March, two 
Chinese fellows completed a year of joint re- 
search in the United States. The first of these 
worked on the biochemistry of atherosclerosis 
and prepared two papers for publication in 
American journals. The topics are the quanti- 
tation of apolipoprotein H in patients with dys- 
lipoproteinemia and the quantitation and dis- 
tribution of apo A-'f in familial dyslipopro- 
teinemia. The second scientist performed cel- 
lular studies of human atherosclerosis at the 
University of Washington in Seattle. 

Two Chinese fellows performed research in 
the NHLBI's Pulmonary Branch with support 
from WHO. The first of these scientists worked 
on defining the role of the eosinophil in inflam- 
matory lung disease and developed an animal 
model useful for studying these diseases. She 
presented her work at the American Thoracic 
Society Meeting in May and an abstract was 
published in the proceedings. The second sci- 
entist worked on elucidating the pathogenesis of 
fibrotic lung disease, one of the principal lung 
diseases in China. 

Egypt 

Discussions of potential exchange activities 
with Egypt continued during FY 1982. A number 



of proposals from Egypt have been received in 
recent years, primarily in hypertension and 
rheumatic heart disease. Informal exchanges of 
experts are underway in hypertension. Two visits 
by Egyptian physicians took place in FY 1982. 
Both experts were interested in the Institute's 
programs in the cardiovascular area and in the 
potential for future cooperation. 

Finland 

U.S. representatives reviewed a draft U.S.- 
Finland Agreement for Health Cooperation de- 
signed to strengthen existing links between the 
scientific communities of the two countries and 
to promote cooperation in health care and bio- 
medical research. Future collaboration will 
include exchanges of specialists and information, 
organization of conferences and lectures, and 
development of joint studies. During a visit to 
the NHLBI by the Secretary General, Ministry of 
Social Affairs and Health of Finland, in October 
1981 the potential of future exchanges in the 
cardiovascular area was discussed. Because 
Finland and the United States are among the 
countries with the highest rates of heart disease 
in the world, both countries are emphasizing 
prevention programs to deal with the problem, 
and, in fact, informal exchanges of specialists 
are underway. 

France 

The pathology of interstitial lung diseases has 
been the focus of a number of joint studies under 
the agreement between the NHLBI and INSERM. 
This agreement was originally signed in 1970, 
and in 1980 a 3-year project on interstitial lung 
diseases was initiated between the NHLBI and 
INSERM. 

During FY 1982, two studies were completed 
and the results submitted for publication: one on 
histiocytic disorders and the other on hypersen- 
sitivity pneumonitis. The first study was based 
on the joint experiences of two French teams 
and one American team. The second study of the 
histological and ultrastructural features of hy- 
persensitivity pneumonitis was based on the 
findings of pooled lung biopsies obtained from 18 
patients. A French scientist visited the United 
States twice for joint experiments. She partic- 
ipated in immunofluorescence studies of the skin 
lesions in sarcoidosis, using monoclonal anti- 
bodies. Upon her return to France, she applied 
the techniques to cells collected by bronchoal- 
veolar lavage as well as to samples obtained 
surgically by open lung biopsies. Two reports are 
being prepared for publication. Two U.S. sci- 
entists made followup visits to Paris to continue 
cooperative studies. 

During FY 1982, the NIH-CNRS program sup- 
ported a joint study to determine the role of the 
natriuretic factor in the initiation and/or main- 



k7 



tenance of essential hypertension in humans. The 
natriuretic factor is a substance in the blood 
that causes excretion of abnormal amounts of 
sodium in the urine. Its structure, function, site 
of formation, and factors causing its release into 
the circulation are unknown. Direct and indirect 
evidence suggests that sodium efflux from white 
blood cells can be inhibited by the plasma of 
hypertensive subjects but not by the plasma of 
normotensive subjects. To confirm these obser- 
vations, U.S. and French scientists are isolating 
the natriuretic factor using new chemical iso- 
lation techniques and bioassay procedures. Dur- 
ing the course of this joint work plasma fractions 
from hypertensive and normotensive patients 
were analyzed. One fraction was found that 
markedly inhibited the enzyme Na-K ATPase. 
Further isolation and purification of the natri- 
uretic factor is planned in order to produce 
monoclonal antibodies that will then be used to 
quantitate the factor in individual plasma sam- 
ples. This work will continue in France. Once 
sufficient quantities of the natriuretic factor are 
prepared, the U.S. laboratory will examine pos- 
sible physiologic roles for the substance and will 
hope to offer new insights into its role in the 
etiology of essential hypertension. 

Federal Republic of Germany 

Cooperative activities in cardiovascular re- 
search are conducted under a joint U.S.-FRG 
agreement between the Department of Health 
and Human Services and the Federal Ministry for 
Research and Technology of the Federal Repub- 
lic of Germany, signed in 1976 and extended for 
5 years in 1981. The emphasis is on linking on- 
going projects in arteriosclerosis and hyper- 
tension. 

During joint scientific and health policy dis- 
cussions held in the FRG in 1981, the following 
cooperative activities were agreed upon for the 
next 2 years: 

• Internationally comparable surveillance and 
monitoring of cardiovascular morbidity and 
mortality and their association with risk 
factors and health practices; 

• Development and exchange of techniques 
and strategies for intervention studies; and 

• Development and exchange of techniques 
for evaluation and validation of approaches 
to intervention. 

Since 1981, U.S. investigators have collabo- 
rated with German scientists in the design and 
planning of a Multicenter Intervention Trial 
(MIT) and the German National Health Survey, 
which will provide the necessary background 
information for the MIT. The German MIT is an 
8-year project. A 5-year trial will be preceded 



by 2 years of pilot studies and followed by 1 year 
of data analysis. To ensure that internationally 
comparable data are obtained, U.S. and FRG 
investigators have agreed to collaborate closely 
throughout the studies. 

Early in FY 1982, a German delegation visited 
the NHLBI, the Central Patient Registry and 
Coordinating Center for the Lipid Research 
Clinics Program, and the National Center for 
Health Statistics. A joint working meeting fo- 
cusing on the German NHS and the MIT was held 
at the NHLBI for a review of the protocols for 
these activities. An in-depth joint analysis was 
performed with special emphasis on standardi- 
zing methods and procedures in the following 
areas: laboratory procedures; electrocardi- 
ography; health behavior assessment including 
nutritional aspects and use of health services; 
assessment of psychological factors; evaluation 
of endpoints; and organization, management, and 
data handling. 

A second German delegation visited the 
NHLBI to develop the syllabus for an advanced 
2-week workshop in epidemiology funded by the 
German Government. This workshop, to be held 
in Germany in the fall of 1983, will be taught by 
a combined U.S.-FRG faculty. The purpose of 
this workshop is to develop the necessary epi- 
demiological skills so that members of the MIT 
staff can produce internationally comparable 
surveillance and monitoring data. Also, late in 
FY 1982, an FRG delegation visited several 
community-based intervention projects in the 
United States to develop and exchange strategies 
for intervention studies and validate their pro- 
posed approaches to intervention. 

Because hypertension is a serious health prob- 
lem in the FRG, as in the United States, the 
German Government is taking steps to bring it 
under control. Several exchanges have taken 
place in this area. Because of the success of the 
American HDFP, the Germans have initiated a 
National High Blood Pressure Education Program 
modeled on the U.S. program. In this way, they 
hope to duplicate some of the declines in car- 
diovascular disease experienced in the United 
States in recent years. A German scientist 
worked for a year with Hypertension Detection 
and FoUowup Program staff in the United States 
to develop the methodology for a pilot study for 
the German equivalent. This cross-sectional 
study, completed in FY 1982, was carried out on 
men and women 30-69 years of age, drawn from 
selected census tracts in Munich. Of the 3,198 
persons selected for the pilot study, 2,216 in- 
dividuals or 70 percent took part. One of every 
three participants was found to be hypertensive 
and nearly half the hypertensives {k5.Z percent) 
did not know of their disease. Of those who 
knew, only half were under treatment and of 
these only one-third had their condition effec- 
tively controlled. In summary, only 11.2 percent 
of the hypertensive patients in the FRG pilot 



^8 



study had their high biood pressure effectively 
controlled at the onset of the program. The 
study results illustrate the seriousness of the 
problem and the feasibility of gathering inter- 
nationally comparable epidemiological data. The 
planned approach is envisioned as a multicenter, 
cooperative, FRG-wide effort aimed at detect- 
ing and treating all Germans who have hyper- 
tension. Several basic research projects in the 
area of hypertension are also being carried out 
by individual U.S. and German investigators 
cooperating informally. 

The FRG Minister of Youth, Family, and 
Health, who visited the NHLBI to discuss ongoing 
cooperative studies with NHLBI staff, showed 
particular interest in Institute programs to con- 
trol hypertension. 



Hungary 

An Umbrella Agreement between the Hungar- 
ian People's Republic and the Government of the 
United States on Cooperation in Culture, Edu- 
cation, Science, and Technology was signed in 
October 1979. The agreement calls for exchange 
and cooperation in areas of mutual benefit and 
common interest. 

Contacts between the United States and Hun- 
gary continued during FY 1982. In July 1982, a 
Summary of Discussion was signed for exchanges 
of scientists in the cardiovascular area. Topics 
include prevention and control of coronary heart 
disease and hypertension, cardiac surgery, dia- 
betes and heart disease, peripheral vascular 
disease, noninvasive and invasive assessment of 
left ventricular function, and pharmacodynamic 
and pharmacokinetic studies with cardiovascular 
drugs. Both sides agreed to exchange up to two 
scientists each year for a total of 4 months. 



India 

The Director-General of the Indian Council of 
Medical Research requested information from 
the NHLBI on the Institute's strategic plan for 
research in cardiovascular disease with a view 
toward implementing a similar plan. The U.S.- 
India Subcommission on Science and Technology 
and Working Group on Medical and Health Sci- 
ences met in December 1981 to discuss potential 
areas of cooperation. A new initiative in scien- 
tific and technological cooperation with India 
was identified in 3uly 1982. The details of the 
initiative will be worked out by a Blue Ribbon 
Panel composed of eminent U.S. and Indian ex- 
perts. The NHLBI has proposed that considera- 
tion be given to rheumatic fever and rheumatic 
heart disease in children, since the incidence of 
these diseases is increasing rapidly in India. The 
diseases, associated with high morbidity and 
mortality, incur high medical costs. 



Israel 

The population of Israel offers unique oppor- 
tunities for epidemiologic research. The diverse 
ethnic and cultural backgrounds of the 3ews who 
migrated there from many countries provide 
important clues to the relative roles of genetics 
and lifestyle in the etiology of cardiovascular 
disease. The NHLBI has funded collaborative 
research with Israel through grants and contracts 
for over a decade. In January 1980, a 5-year 
agreement for cooperation in health was signed 
by the U.S. Department of Health and Human 
Services and the Israeli Ministry of Health, and 
efforts are underway to identify additional op- 
portunities for cooperative activities. 

In 1975, the NHLBI established the Jerusalem 
Lipid Research Clinic to study the prevalence of 
hyperlipoproteinemia among 17-year-old army 
inductees and a subsample of their fathers. This 
clinic, part of the international Lipid Research 
Clinic Program, adheres to highly standardized 
methods of data collection and analysis. The 
Jerusalem population represents 55 countries of 
origin and is divided into four broad groups: 
Israeli, Asian, North African, and European/ 
American. Subject screening was completed in 
1980. 

Preliminary results show important differ- 
ences in blood lipid profiles, which can be cor- 
related with the country of paternal origin. Total 
cholesterol levels were lowest in teenagers of 
North African descent, highest in youths of 
European and Israeli origin, and intermediate in 
those from Asia. Triglyceride levels were lowest 
among North Africans, but Asian and Israeli 
groups had higher values than the Europeans. 
Mean plasma high density lipoprotein cholesterol 
levels were highest among youths with fathers of 
European and American origin and lowest in 
those of Asian and North African descent. Sec- 
ond generation Israelis ranked intermediate 
between the two groups. Thus, patterns of lipid 
and lipoprotein levels previously observed in 
adult immigrants persist into a generation of 
native-born Israelis. These results were consist- 
ent with the observed differences in the dietary 
intake of total fat, saturated fat, and choles- 
teroL The highest intake of these nutrients was 
found in children of native Israeli or European/ 
American fathers. Comparison of the Israeli diet 
with that of a group from the U.S. clinics showed 
relative intakes of fat and saturated fatty acids 
to be lower and carbohydrate higher than in the 
United States. Ischemic heart disease incidence 
and mortality in Israeli ethnic groups correlated 
well with group mean total cholesterol values. 

The results of the Jerusalem study will be 
published as a monograph of the Israel Journal of 
Medical Sciences . Preparation of data analyses 
for this publication was the major effort during 
FY 1982. The monograph will describe lipid and 
lipoprotein profiles by country of origin, dietary 



^9 



patterns, sociodemographic characteristics in 
relation to various cardiovascular risk factors, 
and distribution and characteristics of dyslipo- 
proteinemias in the Jerusalem population. 

Collaborative analyses comparing U.S. and 
Israeli data were begun in September 1982 fol- 
lowing the site visit of a U.S. team to Jerusalem. 
Priority topics include comparisons of food and 
nutrient consumption, diet and plasma lipid and 
lipoprotein associations, incidence of coronary 
heart disease, and resting and exercise ECG 
studies. 

The NHLBI also supports a joint American- 
Israeli Migrant Study of like-sex siblings, one of 
whom migrated to Israel while the other re- 
mained in the United States. Approximately 
2,^00 Israelis and 1,525 North Americans were 
given a complete physical examination to deter- 
mine whether differences in cardiovascular risk 
factors are influenced by genetic and/or envi- 
ronmental factors. Data analyses of this com- 
pleted study are underway. 

Italy 

U.S. -Italy cooperation in cardiovascular re- 
search was initiated in 1978 upon the signing of 
the Joint U.S.-Italy Memorandum of Under- 
standing by the Secretary, DHEW, and the Italian 
Minister of Health in Rome in November 1977. 
The Fifth U.S.-Italy Joint Symposium, entitled 
"Methods of Noninvasive Diagnosis in Cardiovas- 
cular Disease," was held in November 1981 in 
Bethesda, Maryland. The purpose of this meeting 
was to review currently available noninvasive 
techniques and to assess their role and future 
potential in the early diagnosis and monitoring of 
cardiovascular disease. Discussions of imaging 
techniques included comparisons of the levels of 
sensitivity, accuracy, speed, and availability of 
alternative methods as well as the quality of im- 
ages and data produced by different procedures. 

The noninvasive systems reviewed included 
technologies capable of structural, functional, 
biochemical, and mechanical assessment of the 
cardiovascular system in health and disease. 
These systems draw on images and computerized 
data generated by X-ray, radioisotope, ultra- 
sound, and nuclear magnetic response approaches 
that provide information about structures and 
events within the cardiovascular system. For 
each technique, the theoretical basis underlying 
the method, the advantages and disadvantages of 
the procedure, and its current and potential 
capabilities to assess changes in the arterial 
walls were considered. Also, the panel reviewed 
the potential of each technique to assess the 
clinical significance of atherosclerotic lesions as 
evidenced by end organ changes in blood flow, 
metabolism, perfusion, structure, function, and 
mechanical properties. These new methods are 
expected to strengthen preventive and research 
activities in cardiovascular disease and provide 



the necessary information to prove conclusively 
whether a given drug, dietary regimen, surgical 
procedure, or other therapeutic approach has a 
positive effect on the control of this disease. 

During FY 1982, an Italian exchange fellow 
worked for 3 months in the laboratory of a U.S. 
scientist. The joint collaboration supports the 
theory that the endothelium may contribute to 
drug- and hormone-induced vasodilation, perhaps 
through the release of an unidentified endogen- 
ous vasodilator. The investigation is aimed at 
determining the vascular site of action of hy- 
dralazine, a widely used vasodilator and anti- 
hypertensive agent. The results of this collabo- 
rative study indicate that the endothelium may 
play an important role in the vasodilator effect 
of hydralazine. 

The Italian coordinator for the U.S.-Italy 
exchange program visited the NHLBI in 1982 to 
discuss plans for the next joint symposium 
scheduled for the fall of 1983 entitled "Endpoints 
for Cardiovascular Drug Studies," with presen- 
tations addressing chemical, epidemiological, 
and direct observation endpoints. The proceed- 
ings of the U.S.-Italy Joint Symposium on Nutri- 
tion and Cardiovascular Disease are being pub- 
lished by S. Karger AG, Basel. 

A U.S. exchange fellow will work in Italy from 
September to November 1982 to continue the 
joint work on the blood vessel wall in hyperten- 
sion with his Italian counterpart. The visit rep- 
resents a unique opportunity to study this prob- 
lem by means of a bioassay that the Italian sci- 
entist has developed and refined, a "superfusion 
bioassay system" capable of detecting extremely 
low concentrations of substances with musculo- 
tropic activity. 

Japan 

U.S. and Japanese scientists have enjoyed a 
long history of successful informal cooperation 
in the study of cardiovascular diseases. Hyper- 
tension is a major problem in both countries, but 
in Japan the most prevalent sequela is stroke, 
while in the United States heart attack is the 
most frequent outcome. Another point of con- 
trast is in the lipid levels of the two populations, 
which have been increasing steadily in Japan but 
declining in the United States during the last 
decade. The study of these differences is the 
main focus of U.S.- Japanese collaboration. 

A U.S. -Japan Umbrella Agreement in Science 
and Technology in Non-Energy Areas was signed 
in 1980 and includes cooperation in research on 
cardiovascular disease. The agreement provides 
a mechanism for formalizing and expanding the 
joint research that has been in progress between 
the two countries for over a decade. In February 
1982, in the first official meeting under the 1980 
agreement, Japanese and U.S. scientists met to 
discuss and plan the joint activities. Five topics 
were agreed upon for joint investigation: further 



50 



promotion of information exchanges on epide- 
miological and experimental studies of hyper- 
tension; experimental research on the prevention 
of hypertensive diseases, especially nutritional 
prevention and its mechanisms; epidemiological 
analyses on hypertension and related cardio- 
vascular diseases, including the evolution of 
hypercholesterolemia and hypertension in the 
young, and comparison of cerebrovascular and 
cardiovascular diseases; epidemiological analyses 
of risk factors, especially dietary risk factors 
and studies of applicable standardized method- 
ology for assessment of nutritional intake; and 
further exchange of information on community 
health control programs and intervention studies, 
including dietary modification of blood pressure 
control. 

The next U.S.- Japan meeting will be held in 
December 1982 in Japan, where the focus will be 
on discussions of problems in standardizing epi- 
demiological and nutritional studies of hyper- 
tension, as well as experimental studies on the 
prevention of hypertension through nutrition 
control. A joint symposium now planned will give 
U.S. scientists a broader view of Japanese 
research in the field. 

Japanese scientists have developed several 
important animal models for studying hyper- 
tension, atherosclerosis, and hyperlipidemia. 
Recent interest has focused on the Watanabe 
Hereditary Hyperlipidemic rabbit, a particularly 
good model for studying familial hypercholes- 
terolemia. In 1982, NHLBI scientists initiated 
contacts with their Japanese counterparts to 
explore the possibility of further joint study of 
this model. 

NHLBI and Japanese scientists have collabo- 
rated since 1966 on studies involving the Stroke- 
Prone Spontaneously Hypertensive Rat (SHR-SP), 
a model originally developed in Japan. SHR-SP 
animals that were fed the standard NIH rat diet 
had a considerably lower incidence of stroke 
than rats of the same strain that were fed the 
standard Japanese diet. The main difference in 
the diets was in their protein content, and the 
"stroke protection" may be due to an increased 
intake of certain sulphur-containing amino acids 
and aromatic amino acids. Recent human epi- 
demiological studies in Japan have also shown 
the importance of dietary protein in the devel- 
opment of stroke. Other investigators are study- 
ing the role of sodium (Na) and potassium (K), as 
well as the Na:K ratio, in the development of 
hypertension. Japanese and American scientists 
are cooperating on a continuing project entitled 
"Experimental Studies and Dietary Prevention of 
Hypertension and Atherosclerosis," funded by the 
NHLBI and Japanese research institutes. The 
Japanese coinvestigator visited the NHLBI in 
1982 for joint experiments on the preventive 
effect of methionine feeding on the subsequent 
development of hypertensive disease. At the 
Annual Meeting of the Hypertension Specialized 



Centers of Research, he presented some new 
results on the role of sodium and potassium in 
hypertension. One of his findings is on salt- 
accelerated platelet aggregation in general as 
well as in healthy volunteers with a family his- 
tory of hypertension. 

The Honolulu Heart Program, begun in 1970, is 
a 10-year study of prospective coronary heart 
disease and stroke in 8,006 men of Japanese 
ancestry living in Hawaii. On the basis of 10- 
year heart disease incidence and mortality data, 
this population was found to be intermediate 
between the high levels of a similar cohort living 
on the U.S. mainland and the lower levels of one 
living in Japan. However, stroke incidence was 
three times greater in the native Japanese co- 
hort than in the Honolulu sample. The former 
group also had a strong negative correlation 
between cancer (particularly colon cancer) and 
serum cholesterol levels. A 10-year reexamina- 
tion of 2,000 men from the Honolulu sample was 
completed in 1982. Data analyses now underway 
should shed further light on the relative roles of 
genetics and environment in the development of 
cardiovascular disease. 

Kuwait 

An agreement for the U.S.-Kuwait Technical 
Cooperation Program in Health was signed in 
May 1981. In its preparation of a National Health 
Plan, Kuwait is seeking consultant help to devel- 
op a National High Blood Pressure Education 
Program and to carry out epidemiological base- 
line studies and followup monitoring of the pop- 
ulation after disease intervention. Kuwait has a 
relatively high prevalence of hypertension with a 
low control rate and a rapidly increasing cardio- 
vascular death rate. A U.S. consultant who vis- 
ited Kuwait in February 1982 made recommen- 
dations for an improved hypertension control 
program. Next, a Kuwaiti delegation visited the 
NHLBI in March 1982 to discuss the plans for the 
project. The visit to Kuwait of an NHLBI rep- 
resentative in April 1982 then resulted in a pro- 
tocol for improved hypertension control. The 
goals of this effort are to reduce deaths and 
illness associated with uncontrolled hyperten- 
sion, to reduce the proportion of persons at risk 
due to elevated blood pressure, to increase the 
number of health professionals who are trained 
in the use of the recommended hypertension 
management protocol, and to increase the 
Kuwaiti capability to track and evaluate prog- 
ress in hypertension control. 

Nigeria 

An Agreement for U.S. -Nigeria Cooperation in 
Biomedical Research was signed in September 
1981. Cooperative activities with the NHLBI 
have been proposed in hypertension and in sickle 
cell disease. 



51 



Poland 

The NHLBI cooperates with Poland under two 
separate agreements: the U.S.-Polish Agreement 
for Health Cooperation, signed in 1973, and the 
U.S. -Poland Collaborative Research Agreement, 
signed in 1976 and supported by the Marie Sklo- 
dowska-Curie Fund. Activities under the second 
agreement were temporarily suspended during 
FY 1982 because of the political situation. 

Under the 1973 agreement, activities in three 
cooperative areas devoted to basic, clinical, and 
epidemiological research continued in FY 1982. 

Area 1. Basic Research in Etiological Mech- 
anisms; The Metabolic Fate and Function of 
Prostacyclin.— Prostacyclin, a vasodilatory 
prostaglandin produced in the arteries, is thought 
to be important in preventing the formation of 
blood clots. Prostaglandins also seem to affect 
the circulation as mediators of hormone systems; 
thus, their role in hypertension is under intense 
investigation. From November 1981 to January 
1982, a Polish scientist continued joint pharma- 
cologic research in the United States on platelet 
aggregation techniques and prostacyclin metab- 
olites. It had previously been reported that an 
enzyme present in platelets transforms the labile 
antiaggregatory compound, prostacyclin (PGI2), 
to a more stable compound, S-keto-PGEj. The 
present study was directed toward characteri- 
zing a previously unrecognized intermediate in 
this pathway. It is hypothesized that the anti- 
aggregatory activity of PGI2 may be due to this 
unknown intermediate substance. This work is 
important to our understanding of thrombosis 
and to the development of drugs to prevent it. 

Area 2. Clinical Research; The Diagnosis and 
Treatment of Cardiomiopathy .— Plans were made 
for the U.S. coordinator to spend 1 month in 
Poland next year for continued joint inves- 
tigations. 

Area 3« EpidemioloRJcal Research; The Car - 
diovascular and Clinical Correlates of High- 
Density Lipoproteins .~A cooperative study has 
been set up to explore the differences in cardi- 
ovascular disease and risk factor trends between 
Poland and the United States. Nearly 5,000 men 
and women aged 35-6't will be screened in War- 
saw and Cracow. The U.S. and Polish coordin- 
ators met in October 1981 to discuss the pro- 
posed study design and protocol; agreement was 
reached on all the elements that will be studied. 
A final study protocol is now being developed. 
Two Polish scientists will visit the United States 
in the fall of 1982 to learn laboratory standard- 
ization procedures and to study methods of 
lipoprotein measurement for use in the joint 
study. 

Under the U.S.-Poland Collaborative Research 
Agreement, the NHLBI has supported two sepa- 



rate studies. The first of these is the Polish Trial 
in Multifactorial Prevention of Coronary Heart 
Disease, part of a WHO-sponsored European 
trial. During the U.S. coordinator's visit to Po- 
land in May 1982, the results of the preventive 
program to reduce coronary heart disease risk 
factors in selected factory workers were ob- 
tained and reviewed. The reduction of coronary 
heart disease risk factors in high-risk men was 
greater than in the general factory population. 
Other data analyses are underway. 

The second activity in progress under this 
agreement is the Followup Study of Chronic 
Nonspecific Respiratory Disease, to be made in 
Cracow. This 13-year prospective study is ex- 
pected to yield important data on this disease. 

Spain 

A 5-year Treaty of Friendship and Cooperation 
between Spain and the United States was signed 
in January 1976 and renewed in FY 1982. The 
NHLBI has expressed interest in collaboration in 
cardiovascular diseases and in blood banking and 
blood resources. 

Sweden 

In FY 1982 exchanges between the United 
States and Sweden focused on bringing U.S. and 
Swedish investigators together for discussions of 
data bases of potential interest to both nations. 
Data on patients with Pi.ZZ emphysema, a very 
rare disease, have been collected in both coun- 
tries. By collecting as much information as pos- 
sible on this combined group of patients, sci- 
entists hope to learn more about the course of 
this disease and the benefits of treatment. 

United Kingdom 

During FY 1982 data collection was completed 
on the British Norwegian Migrant Study, in which 
73,88^^ men and women in the United States, 
Britain, and Norway were surveyed by mail to 
determine the prevalence of angina and other 
cardiorespiratory symptoms. A publication cur- 
rently in press reports the analysis of factors 
associated with angina-related mortality. Other 
research being prepared for publication concerns 
mortality differentials due to cigarette smoking 
and mortality differentials due to cardiores- 
piratory symptoms. Persons remaining in Britain 
and Norway reported the symptom of angina 
more frequently than did the migrants to the 
United States. During a 5-year period following 
the survey, angina was found to be a strong 
predictor of cardiovascular mortality. In the 
absence of angina, the migrants had a mortality 
rate similar to nonmigrants, regardless of coun- 
try of origin. However, the British had higher 
mortality rates from cardiovascular and non- 
cardiovascular causes than did the Norwegians. 



52 



The primary determinant of angina prevalence 
was found to be migration status. It is believed 
that those who migrated constitute a healthier 
group than those who did not migrate. 

U.S.S.R. 

During FY 1982, U.S.-U.S.S.R. cooperation 
continued under the bilateral health agreement 
signed in 1972 and renewed in 1977 and 1982. 
Cooperation is underway in eight areas of mutual 
interest and need. During the 10 years of coop- 
eration, 54^ specialists were exchanged. More 
than 100 U.S. and Soviet institutions have par- 
ticipated in the exchange, more than 60 in the 
United States and ^0 in the U.S.S.R. Twenty-two 
joint symposia have been held, and the proceed- 
ings have been published (or are being prepared 
for publication) in both English and Russian. 
Nearly 700 scientific reports, abstracts, and 
related articles have been published under the 
auspices of the exchange. 

Area 1. Pathogenesis of Atherosclerosis .— 
This is a multidisciplinary, multiclinic research 
program on the metabolism and epidemiology of 
plasma lipids and lipoproteins as they relate to 
atherosclerotic disease. The collaboration is an 
extension of the NHLBI-sponsored Lipid Re- 
search Clinics Program; it involves the partic- 
ipation of nine U.S. lipid research clinics and two 
clinics in the U.S.S.R. (Moscow and Leningrad). 
In addition to geographic diversity, the popula- 
tions selected for joint study in both countries 
cover broad ethnic, occupational, and age ranges 
making a variety of cross-cultural comparisons 
possible. Important differences in cardiovascular 
risk factors between the Soviet and American 
study populations have emerged. The possible 
causes of these differences are being explored to 
clarify further the relationship between 
cardiovascular risk factors and deaths in both 
countries. 

Extensive information has been collected and 
analyzed on the prevalence of hyperlipopro- 
teinemia in men ages W-59. The results were 
presented at the First Joint Lipoprotein Sympo- 
sium in May 1981 and will be published in both 
countries late in 1982. A 5-year followup to 
determine the cardiovascular status in a selected 
subsample of these middle-aged men is now in 
progress. A second prevalence study on a broader 
population sample, men and women ages 20-69, 
was initiated in 1978. Subject screening in this 
phase was completed in May 1982. All the data 
have been collected by rigorously trained per- 
sonnel according to common protocols, using 
highly standardized laboratory and screening 
techniques. 

In May 1982, the results of the first preva- 
lence study on middle-aged U.S. and U.S.S.R. 
men were presented at the Sixth International 
Symposium on Atherosclerosis in Berlin. The 



distributions of plasma total cholesterol, tri- 
glycerides, and high density lipoprotein (HDL) 
cholesterol differ significantly between the U.S. 
and U.S.S.R. sample populations. Both the ^^0-^9 
and 50-59 year age groups in the U.S.S.R. had 
significantly higher mean values for plasma total 
cholesterol and significantly lower mean plasma 
triglyceride values. The higher mean levels of 
plasma total cholesterol in the U.S.S.R. sample 
may be attributable in part to the higher con- 
sumption of dietary cholesterol and saturated fat 
and to the lower consumption of polyunsaturated 
fat in that country compared to the United 
States. This difference in consumption patterns 
may also account for the higher triglyceride 
levels found in the U.S. sample. Both U.S.S.R. 
age groups also had significantly higher HDL 
cholesterol levels. This form of cholesterol has 
been associated with a decreased risk of coron- 
ary heart disease. The U.S.S.R. ^0-49 year age 
group also had significantly higher mean low 
density lipoprotein (LDL) cholesterol values. 
LDL has a strong positive relationship to coron- 
ary heart disease. The higher mean HDL choles- 
terol levels in the U.S.S.R. may reflect an 
aggregate of environmental factors. 

The association of HDL cholesterol with other 
cardiovascular risk factors was also studied. In 
both countries, lower HDL cholesterol levels 
were associated with obesity and carbohydrate 
consumption, while moderate alcohol consump- 
tion was associated with higher levels. Other 
population studies have demonstrated that HDL 
cholesterol levels are lower in cigarette smokers 
than in nonsmokers. The findings here show that 
the U.S. data support this link, while in the 
Soviet men the association was either nonsig- 
nificant or weak. Further investigation of these 
differences is planned. 

During the visit of a U.S. scientist to the 
U.S.S.R. in November 1981, drafts of three joint 
manuscripts were developed from data presented 
at the First 3oint Lipoprotein Symposium. Data 
analysis is also underway on blood pressure, 
clinical chemistry tests, smoking, and exercise 
electrocardiogram findings. A paper entitled 
"U.S.S.R. and U.S. Nutrient Intake, Plasma 
Lipids, Lipoproteins, and Nutrients in Men Ages 
40-59 Sampled From Lipid Research Clinics 
(LRC) Populations" will be presented at the 
American Heart Association meetings in Novem- 
ber 1982. The findings show that the Soviet men 
had higher dietary intake of kilocalories, satur- 
ated fats, cholesterol, and carbohydrates, while 
the American men had greater values for pro- 
tein, fat, and polyunsaturated fatty acids. 

A U.S. working group visited Moscow and 
Leningrad in December 1981 to review screening 
procedures in the prevalence study; data col- 
lection and mortality classification procedures in 
the followup study were also discussed. A Soviet 
biochemist visited the United States for 2 
months to work on independent studies of HDL 



53 



subfractionation and on the composition and 
function of HDL apoproteins. 

The large investment of resources in this 
collaborative area is now producing tangible 
results. Eight years of data collection have cul- 
minated this year in the completion of subject 
screening and observation of important contrasts 
between the U.S. and U.S.S.R. study populations. 
Future plans include continued analysis of data 
from the second prevalence study and continu- 
ation of the 5-year followup study. A new em- 
phasis on basic research is planned to investigate 
questions raised by the epidemiological findings. 
Directions for this research will be developed at 
the next 3oint Steering Committee meeting. 



differential intensive medical care in the 
U.S.S.R. in the intensively treated patient groups 
who also share similar initial characteristics. 

The data on all patients in both the United 
States and the U.S.S.R. are stored in the com- 
puter facilities at the Data Coordinating Center 
in Seattle. The study protocol specifies patient 
followup through 3une 1983. Followup data on 
the clinical status of the sample are forwarded 
to the Coordinating Center twice a year. Com- 
pletion of initial analyses of the data is antici- 
pated by the fall of 1982 when a joint working 
meeting will be held in Moscow. Those attending 
this meeting will review and evaluate the data 
from the joint study, interpret preliminary 
results, and discuss opportunities for further 
cooperation. 



Area 2. Management of Ischemic Heart 
Disease .— During FY 1982, cooperation con- 
tinued on the collection and analysis of data on 
American and Soviet patients participating in 
joint studies of different approaches to the man- 
agement of advanced coronary heart disease. 
The therapies under investigation include "dif- 
ferential" intensive medical management in the 
U.S.S.R., "conventional" standardized medical 
management in both countries, and coronary 
bypass surgery in the United States. The study 
includes a total of 1,648 patients carefully se- 
lected according to joint criteria. Approximately 
one-third of the patients are from the Soviet 
Union, and two-thirds are from the United States. 

One group of patients in both the United 
States and the U.S.S.R. is precisely described by 
symptoms, coronary angiograms, and a variety of 
other characteristics. These patients, who con- 
stitute the "reference" groups, are being treated 
by conventional methods. Another group of pa- 
tients with somewhat different coronary angio- 
graphic characteristics is being treated in the 
United States by coronary artery surgery and in 
the U.S.S.R. by differential "intensive" medical 
management. The "reference" group in each 
country and the two "intensively treated" groups 
are each composed of men from 30 to 60 years 
of age. In the United States, the joint study 
includes analysis of data from patients under- 
going surgical treatment who have one or more 
coronary arteries occluded by lesions causing an 
obstruction greater than 70 percent. In the 
Soviet Union, data are analyzed from patients 
with comparable heart disease who are treated 
by a specialized pharmacological regimen. 

The joint study of these American and Soviet 
patients will assess whether subjects in the ref- 
erence group in both countries, who met the 
same criteria and are treated in a generally 
similar fashion, have similar characteristics on 
admission and similar outcome on long-term 
followup. If this similarity does exist, then there 
will be a basis for comparing the long-term 
effects of surgery in the United States with 



Area 3. Myocardial Metabolism .— Basic 
research to develop information that may lead to 
improved methods for prevention and treatment 
of cardiac diseases is the objective of Area 3. 
3oint studies are underway on the mechanisms of 
energy transfer within cardiac cells and on the 
ways that these cells respond to oxygen defi- 
ciency. Other studies concern the factors that 
regulate cardiac growth, the coordination of 
contraction within cardiac cells, the response of 
cardiac cells to changes in their microenviron- 
ment, the visualization of cardiac muscle dam- 
age due to oxygen deficiency, and the effective 
rapid transport of drugs to damaged heart 
muscle. 

Teams of American and Soviet collaborators 
have carried out joint research projects spanning 
a number of years. The research is carried out 
jointly in U.S. and U.S.S.R. laboratories, enabling 
both sides to contribute techniques unique to 
their respective countries. As a result, new 
information has become available more rapidly 
than would have been possible without such 
cooperation. The English language proceedings of 
the Fifth U.S.-U.S.S.R. Symposium, which were 
published in FY 1982, contain reports on the 
cooperative projects. Also during this year, 
several joint articles have appeared in major 
U.S. and Soviet journals. Titles include "Ca2+- 
Dependent Interaction of 5-Dimethylamino- 
naphthalene-1-Sulfonyl Calmodulin with Cyclic 
Nucleotide Phosphodiesterase Calcineurin and 
Troponin I," "A Study of Actin Fibronectin In- 
teraction," "Chromatographic Studies on Inter- 
conversions of 'Non-Activated' and 'Activated' 
Forms of Glucocorticoid Receptor Complexes 
from Rat Heart Cytosal," and "A Structural 
Study of Filamin, a High-Molecular-Weight 
Actin-Binding Protein From Chicken Gizzard." 

Three U.S. scientists conducted joint research 
in the U.S.S.R. in FY 1982. One worked on 
lipoprotein genes and on the effect of gluco- 
corticoids on myocardial calcium metabolism. 
3oint research protocols were drafted, and a 



5tt 



jointly authored article was prepared. The sec- 
ond U.S. scientist continued joint research and 
completed a joint publication, entitled "Creatine 
Kinase of Heart Mitochondria: Changes in Its 
Kinetic Properties Induced by Coupling to Oxi- 
dative Phosphorylation." Both scientists made 
presentations at the Ninth World Congress of 
Cardiology in Moscow. A third U.S. scientist 
continued joint work on structural proteins of 
cells, including studies on spectrin. He prepared 
and took to the Soviet Union a large quantity of 
pure spectrin, a cytoskeletal protein of red blood 
cells. The collaborating Soviet scientist con- 
ducted physical chemistry studies on this protein. 

Two Soviet scientists visited the United States 
during FY 1982. One continued joint studies on 
targeted drug transport to damaged cardiac cells 
employing drug-loaded liposomes. In 1978, the 
Soviet investigator together with a U.S. col- 
league succeeded in linking antibodies specific 
for cardiac myosin to liposomes. When cardiac 
muscle is damaged by lack of oxygen, intra- 
cellular antigens are uncovered that are recog- 
nized by this liposome-antibody complex. By 
adding an isotopic marker to the drug liposome 
complex, scientists can visualize the damaged 
muscle at the same time as the therapeutic 
agent is rapidly and preferentially applied to it. 
Results of these joint studies have been pub- 
lished in major U.S. and Soviet journals. A sec- 
ond application of the Soviet-developed lipo- 
somes is being studied both in the United States 
and the U.S.S.R. A U.S. biochemist has syn- 
thesized a potent renin inhibitor to be used as a 
potential antihypertensive agent. However, this 
peptide is metabolized within minutes after 
injection into laboratory animals. It is hoped that 
this breakdown of the active compound can be 
delayed by encapsulating it into liposomes. The 
U.S.-developed peptide has been sent to the 
U.S.S.R., where it will be linked to liposomes. 
These collaborative studies are aimed at the 
development of a long-acting injectable renin 
inhibitor suitable for use in the treatment of 
hypertension. The other Soviet scientist studied 
advanced nuclear magnetic resonance techniques 
to measure metabolism in the intact heart and to 
begin a joint research project in this area. 

Three senior U.S. investigators visited the 
U.S.S.R. in 1982 to present papers and exchange 
research findings in areas of mutual interest. 
The topics included regulation of protein turn- 
over in skeletal and heart muscle, regulation of 
amino-acid catabolism, regulation of microtu- 
bule assembly and distribution in eukaryotic 
cells, calcium regulation of cytoskeletal func- 
tions, mechanisms of mitosis and chromosome 
movement in eukaryotic cells, molecular dif- 
ferentiation of the myocardium, and the mech- 
anism of heart morphogenesis. Also, the U.S. 
coordinator for Area 3 visited the U.S.S.R. to 
plan the next joint symposium to be held there in 
1983. 



Area 4. Congenital Heart Disease .— Coop- 
erative activities in this area center on the 
surgical treatment of complex heart defects as 
well as on methods of diagnosis and postopera- 
tive care to reduce mortality from congenital 
heart disease. 

A three-member Soviet delegation including 
the U.S.S.R. Coordinator for Area ^ visited the 
United States and met with U.S. counterparts to 
discuss plans for further cooperation and to 
review the results of the latest research on this 
cardiovascular disease problem. Plans were made 
for the Fifth Joint U.S. -U.S.S.R. Symposium on 
Congenital Heart Disease to be held in May 1983 
in the United States. 

Surgical techniques were discussed during the 
delegation's visit to U.S. clinics and cardiovas- 
cular centers. Both sides reviewed their exper- 
iences with heart transplants and surgical pro- 
cedures to control arrhythmia. The Soviets have 
an active surgical program for arrhythmia, and 
interest was expressed in joint discussions of 
indications for surgery and also of valve re- 
placement as possible topics for future joint 
collaborative activities. 

In 3uly 1982, a U.S. scientist visited the 
U.S.S.R. to meet with the U.S.S.R. Coordinator 
for joint discussions on cardiorespiratory physi- 
ology and postoperative care. He lectured at 
Soviet medical institutions on the topics of acute 
respiratory failure, postoperative respiratory 
failure, and general principles of intensive care 
of the critically ill patient. 

Area 5. Sudden Death .— A disturbance in heart 
rhythm is believed to be the immediate 
mechanism of sudden death, which constitutes a 
leading cause of mortality in the United States 
as well as in the U.S.S.R. U.S.-U.S.S.R. collab- 
oration is designed to learn more about the 
mechanisms of arrhythmias and about the inter- 
vention of antiarrhythmic agents to regulate the 
heart's electrophysiologic functions. 

During FY 1982, joint activities included the 
Third Joint U.S.-U.S.S.R. Symposium on Sudden 
Death held in Kaunas, Lithuania, June 1982. In 
December 1981, the U.S.S.R. coordinator and his 
colleague from Kaunas visited the United States 
to complete plans for the symposium. An eight- 
member U.S. delegation participated in the 
symposium and also attended the Ninth World 
Congress of Cardiology in Moscow. Symposium 
topics included recognition of risk associated 
with arrhythmias, reversible coronary artery 
obstruction, pathobiology of acute myocardial 
ischemia, sensory functions of the heart, modu- 
lation of adrenergic activity of the heart, vari- 
ations in morphology of the atrioventricular node 
and His bundle of the human heart, neurological 
and humoral aspects of sudden death, and the 
possible protective effect of neuropeptides in 
animals susceptible to sudden death when placed 
in conflict situations. A joint paper was pre- 



55 



sented on an ongoing exchange of epidemiolog- 
ical data to determine if certain populations in 
each country may provide a "laboratory" for 
investigating national mortality trends in each 
country. The U.S. investigators had learned that 
in local areas time trends of the incidence of 
acute myocardial infarction, one of the most 
important clinical components of ischemic heart 
disease (IHD), parallel national mortality trends. 
The joint presentation reported the results of 
investigations of data from medical histories and 
from clinical, electrocardiogram, and laboratory 
studies of patients with acute myocardial in- 
farction in Oakland, California, and compared 
these data with those of patients included in the 
registry of acute myocardial infarction in 
Kaunas, Lithuania. A number of differences were 
noted in electrocardiographic and serum enzyme 
studies. Nevertheless, percentages of cases 
classified as definite and possible acute myocar- 
dial infarction among the U.S. and Kaunas 
patients were similar. Through the study and 
comparison of long-term trends in the two na- 
tions, we expect a better understanding of the 
factors affecting development of ischemic heart 
disease and sudden death. 

Further exchanges of scientists are planned in 
six areas: pathological anatomy, electrophysi- 
ology of sudden death, study of the effects of 
antiarrhythmic drugs, clinical aspects of sudden 
death, epidemiology of sudden death, and higher 
nervous and peripheral nervous activity in ven- 
tricular arrhythmias and sudden death. 

Area 6. Blood Transfusion .~The exchange in 
Area 6 focuses on research on blood and blood 
products for transfusion and treatment of dis- 
ease. In the past, the emphasis in Area 6 has 
been on hepatitis, posttransfusion hematological 
complications, and blood substitutes. However, 
in recent years the range of collaboration has 
broadened, encompassing thrombosis and hemo- 
stasis in general, with particular emphasis on 
platelet abnormalities as well as on hemophilia 
and other genetic bleeding disorders. 

In December 1981, a three-member Soviet 
delegation visited the United States to exchange 
information and data on procedures for blood 
donor processing, blood components, and prep- 
aration of platelet concentrations. U.S. and 
Soviet scientists discussed a possible joint proj- 
ect for isolating and studying vesicles shed by 
red cells during storage and for quantitative 
analysis of their membrane proteins. It was 
agreed that prior to shipping specimens from the 
U.S.S.R. to the United States, preliminary 
studies on the stability of vesicle preparations 
would be completed in Moscow. In the area of 
hepatitis, the Soviets are studying the specific 
immunology of anti-A as well as anti-B 
hepatitis. The visit of the Soviet delegation 
provided opportunities to discuss future collab- 
oration on the use of Factor VIII in the treat- 



ment of hemophilia, red blood cell preservation, 
and long-term preservation of platelets. 

A U.S. scientist visited the Soviet Union in 
April 1982 to lecture on genetics and hemoglob- 
inopathies and to discuss modern laboratory 
techniques of gene manipulation. The visit pro- 
vided an opportunity for the Soviet Central 
Institute of Hematology and Blood Transfusion 
and the NHLBI to exchange information on cur- 
rent developments in molecular biology research 
on thalassemia and to plan future collaborative 
activities. 

During the fall of 1982, a U.S. scientist visited 
the U.S.S.R. to continue joint studies in the area 
of hematapheresis. This collaboration compared 
platelet collection procedures and patient trans- 
fusion response to platelets collected by con- 
tinuous flow cell separation techniques; com- 
pared recipient response to leukocyte-rich single 
donor platelets ("Aminco") and leukocyte- 
depleted platelet ("IBM-2997") concentrates and 
patient response; measured efficiency of cyto- 
reduction procedures using "Aminco" and "IBM- 
2997" blood cell separators in patients with blood 
diseases (thrombocytosis and leukocytosis); and 
determined the frequency of leukapheresis and 
platelet pheresis to reduce risks of cerebrovas- 
cular accidents. 

The new U.S.S.R. chairman for Area 6 and his 
U.S. counterpart met in August 1982 during 
meetings of the International Hematology and 
Blood Transfusion Societies to discuss plans for 
exchanges and studies. These plans will be de- 
veloped further during the Ninth Working Meet- 
ing in Area 6 scheduled for December 1982 in 
the United States. At that time, the U.S. and 
U.S.S.R. representatives will also plan the pro- 
posed program of the Third Joint Symposium on 
Blood Transfusion to be held in the U.S.S.R. in 
1983. 

Area 7. Hypertension .— Begun in 1977, joint 
activities in this area have focused on the ex- 
change of information, exchanges of scientists, 
joint working meetings, and joint symposia on 
the clinical, psychophysiological, behavioral, 
epidemiological, and preventive aspects of 
hypertension. 

The Proceedings of the 1981 Joint U.S.- 
U.S.S.R. Symposium on Hypertension; Biobe - 
havioral and Epidemiological Aspects are cur- 
rently being prepared by the U.S. side for pub- 
lication in English and by the Soviet side for 
publication in Russian. They will include 10 
Soviet papers and 7 U.S. papers. 

In July 1982, two U.S. scientists visited the 
U.S.S.R. to develop plans for a joint study on 
psychological interventions and the role of the 
sympathetic nervous system in primary hyper- 
tension. This collaborative study assesses neur- 
oendocrine and blood pressure changes resulting 
from biobehavioral treatment strategies. Spe- 
cifically, the study will determine if nonpharm- 



56 



acological interventions (hypnosis, biofeedback, 
transcendental meditation, and relaxation tech- 
niques developed by the Soviet side) can reduce 
blood pressure in patients with primary hyper- 
tension classified according to psychological 
profiles developed in the United States. 

In accordance with the Summary of Discus- 
sions signed at the 1981 symposium, a joint 
working meeting on biobehavioral treatment of 
hypertension is scheduled for the fall of 1982 in 
the U.S.S.R. Three topics of collaboration are 
being developed in this area— basic, clinical, and 
community intervention studies. In each of these 
areas, resource groups of experts have been 
identified to facilitate future scientific ex- 
changes and to develop a productive exchange 
program between U.S. and Soviet laboratories. 

Area 8. Artificial Heart Research and Devel - 
opment. — U.S.-U.S.S.R. collaboration in the 
development of artificial heart and circulatory 
assist systems recognizes that present and 
foreseeable treatments still leave a substantial 
number of patients with compromised or fatally 
impaired heart function. The development of 
supportive mechanical devices to assume some 
and eventually all of the pumping function of the 
failing heart is the long-term goal of this coop- 
eration. 

During April 1982, the U.S.S.R. Chairman for 
Artificial Heart Research and Development 
visited the United States to discuss mechanically 
assisted circulation. Six areas of proposed coop- 
eration were identified: the study of the mech- 
anisms of interaction of biomaterials with blood 
and its components and the development of 
comparability criteria for evaluating biomater- 
ials' hemocompatibility; comparative evaluation 
of the condition of the myocardium by means of 
biochemical and morphological tests during 
one- or two-sided bypass; comparative evalua- 
tion and development of new methods of con- 
necting various pump devices for two-sided 
bypass; exchanges of specialists and delegations 
in order to continue further joint activities in 
assisted circulation, artificial heart control 
systems, and biomaterials; publication of joint 
articles on U.S.-U.S.S.R. activities and scientific 
data exchanges; and plans for the Third and 
Fourth U.S.-U.S.S.R. Symposia on Artificial 
Heart and Assisted Circulation in the U.S.S.R. in 
1983 and in the United States in 1985. 

Two publications were generated from U.S.- 
U.S.S.R. cooperation in this area during FY 1982. 
A joint paper entitled " In Vitro Evaluation of 
U.S. and U.S.S.R. Artificial Hearts" was pub- 
lished in Artificial Organs , the journal of the 
International Society of Artificial Organs, in 
May 1982. A Soviet article describing an im- 
plantable artificial heart driven by a compact 
motor was received by the U.S. side and trans- 
lated for review by U.S. investigators. 

In accordance with a previous agreement, the 



U.S. side provided the U.S.S.R. counterparts with 
biomaterials in exchange for the control system 
received from the U.S.S.R. in 1981. Plans for the 
future call for continued exchanges of scientists 
from each side to conduct joint in-depth evalu- 
ation of the blood compatibility of several fre- 
quently used biomedical polymers by means of in 
vitro techniques. 

One of the outcomes of U.S.-U.S.S.R. coop- 
eration in the cardiovascular area is the publi- 
cation of the Journal of Soviet Cardiovascular 
Research , published by Plenum Press. This Eng- 
lish language journal, now in its third year of 
publication, contains articles translated from 
Kardiologia and other Soviet journals on the best 
Soviet research in the cardiovascular area. 
Articles are selected by an editorial board com- 
posed of U.S. and Soviet scientists, including 
several of the coordinators for the eight areas of 
U.S.-U.S.S.R. cooperation in the cardiovascular 
field. 

Venezuela 

A Joint U.S. -Venezuela Science and Technol- 
ogy Agreement was signed in October 1979. 
Venezuelan scientists have a strong interest in 
cooperation in the cardiovascular area, partic- 
ularly in clinical research. Possible collaborative 
efforts are being considered in Chagas' disease, 
which is endemic in rural areas of Venezuela and 
in other South American countries. Chagas' 
disease infects children at an early age, and a 
large proportion of these patients develop car- 
diomyopathy several years later. 

Venezuelan and NHLBI investigators are de- 
veloping a protocol to study Chagas' disease. 
During FY 1982, the director of the Venezuelan 
institute established to prevent, detect, and 
treat this disease worked with NHLBI epidemi- 
ologists on protocol development, data handling 
methodology, and the design of instruments to be 
used in this study. Later in FY 1982, the Direc- 
tor, Centro Pan Americano de la Investigacion y 
Adiestramiento de Enfermedades Tropicales 
(CEPIALET), who is also the Venezuelan coor- 
dinator for the U.S.A.-Venezuela Cooperative 
Agreement, visited the NHLBI to discuss the 
Chagas' project with Institute staff. 

Venezuela is one of the countries interested in 
developing uniform international standards for 
the biomaterials used for human prostheses. To 
facilitate both national and international stand- 
ardization, the NHLBI has produced biomaterial 
standards for distribution to interested inves- 
tigators. Samples of these U.S. biomaterial 
standards have been requested by Venezuelan 
investigators. 

Yugoslavia 

Coronary heart disease (CHD) can result from 
the interaction of a number of environmental, 



51 



behavioral, genetic, and physiological factors. 
Because Yugoslavia is undergoing rapid indus- 
trialization, scientists are concerned about in- 
creased coronary heart disease. 

Several studies on this problem have begun as 
a result of the agreement signed between the 
United States and Yugoslavia in 1973. During FY 
1982, plans were completed for a study entitled 
"An Epidemiological Study of Secular Trends in 
CHD Risk Factors." This study uses data from a 
population in Tuzla, a suburb of Zagreb, pre- 
viously studied for many years under the project 
"Incidence of Hypertension and Coronary Heart 
Disease." The objectives of the new study are to 
determine whether cigarette smoking, hyper- 
tension, and electrocardiographic abnormalities 
are increasing in Yugoslavia. The study will 
include a repeat examination of part of the 
original cohort in Tuzla, as well as an examina- 
tion of two younger cohorts (aged 35-^^^), one in 
Tuzla and one in Belgrade. Two U.S. scientists 
visited Yugoslavia in April and May 1982 to 
discuss technical aspects of the study to ensure 
comparability of the Yugoslav data with U.S. 
data. The computer capabilities of the Institute 
of Chronic Diseases and Gerontology in Belgrade 
were reviewed as well as procedures for data 
analysis. 

By measuring risk factors over an extended 
period of time in cohorts of similar age, this 
study will examine whether the industrialization 
and urbanization process is accompanied by 
changes in physiological characteristics. It will 
also provide information on changes in the prev- 
alence of CHD. If an increase in CHD is ob- 
served, the study will ascertain how much might 
be due to changes in the known risk factors. The 
study will also seek to determine which changes 
in the study population's environment are the 
most important for developing CHD. 

Cooperation With International Agencies 

During FY 1982, the NHLBI continued its 
active cooperation with international agencies. 
Since 1980, the Institute has been a WHO Re- 
gional Collaborative Center for Research and 
Training in Cardiovascular Diseases for the 
Americas. In this capacity, the NHLBI provides 
advisory services for WHO, and collects and 
exchanges information on cardiovascular dis- 
eases. The Institute also assists in the place- 
ment of WHO-sponsored fellows from different 
countries. 

The NHLBI is collaborating with WHO on the 
Multinational Monitoring of Trends and Deter- 
minants in Cardiovascular Diseases (MONICA), a 
new health information system to measure heart 
disease incidence by collecting longitudinal, 
cross-cultural data on cardiovascular disease risk 
factors. NHLBI epidemiologists assisted in 
designing the study protocol. Pilot studies were 
completed in 1981 in four communities where 



the formal study is now underway. Other 
MONICA'S will be launched in 1983 in eight 
additional countries. 

Plans for other cooperative activities between 
the NHLBI and WHO were considered. In 3uly 
1982, the WHO representative for genetic dis- 
eases met with NHLBI staff to discuss possible 
future collaboration on sickle cell disease. WHO 
is interested in implementing programs in Africa 
to address this problem. The Chief of Cardio- 
vascular Diseases at WHO visited the NHLBI in 
April 1982 to discuss areas of continuing coop- 
eration. The Assistant Director for International 
Programs, NHLBI, met with WHO officials in 
Geneva to discuss its programs on cardiovascular 
disease prevention and control. 

The NHLBI and WHO have also exchanged 
information concerning WHO's Integrated Pro- 
gram for the Prevention and Control of Noncom- 
municable Diseases. The objective of this pro- 
gram is to improve the health of total communi- 
ties with respect to noncommunicable diseases 
through an integrated approach to health pro- 
motion. The NHLBI has provided WHO with 
information on its intervention and health edu- 
cation programs relevant to the WHO effort. 

At the request of PAHO, Institute staff par- 
ticipated in a workshop entitled "Contribution of 
Dietary and Pharmacological Interventions in the 
Prevention and Control of Cardiovascular Dis- 
eases" in March 1982. This workshop brought 
together investigators from Brazil, Chile, Ecua- 
dor, Jamaica, Mexico, and Trinidad to plan the 
project. Responding to a number of questions 
regarding the proposed design of the study, In- 
stitute staff gave advice based on Institute ex- 
perience with similar projects. Among the 
questions discussed was the strength of the evi- 
dence that an increased intake of polyunsatur- 
ated fatty acids coupled with a decreased intake 
of saturated fatty acids to bring the dietary 
ratio close to 1 (P/S ratio = 1) results in both 
lowering blood pressure (systolic and diastolic) in 
normal as well as in mildly hypertensive popu- 
lations and reducing the tendency to thrombosis. 

Two PAHO fellows from Thailand visited the 
NHLBI in May 1982, one of whom is the Chair- 
man for Planning and Organization for Preven- 
tion and Control of Cardiovascular Disease in 
Thailand. They toured U.S. medical and research 
facilities to study the planning, organization, and 
research aspects of the prevention and control of 
cardiovascular disease. Also, in FY 1982 two 
U.S. scientists—one individually and the other as 
part of a WHO team—visited Thailand to con- 
tinue joint scientific discussions. 

Extramural Programs 

During FY 1982, the NHLBI awarded 6 con- 
tracts and 17 grants to the following countries: 
Argentina, Australia, Canada, Denmark, Israel, 



58 



Romania, and Sweden. These awards supported 
mainly cooperative epidemiological studies on 
foreign components of national clinical trials. 
Ten fellowships were awarded to U.S. scientists 
for training in the following countries: Belgium, 
Canada, Israel, Sweden, Switzerland, and the 
United Kingdom. These young American re- 
searchers took their training outside the United 
States to capitalize on unique research oppor- 
tunities available in chosen foreign institutions. 

Human red blood cell production is basically 
under the control of the erythropoietin hormone. 
Extensive studies of this hormone are underway 
in the United States. These studies require hu- 
man erythropoietin, which is best obtained from 
the urine of anemic patients. In certain areas of 
Argentina, iron-deficient anemia due to hook- 
worm is endemic. The NHLBl is supporting the 
collection, purification, and study of this hor- 
mone from these patients. The Institute also 
makes available erythropoietin for study by U.S. 
researchers. 

The Institute is supporting research on the 
genetic epidemiology of precursors of human 
hypertension in a migrant Polynesian population. 
This longitudinal study is designed to identify 
factors that cause an increase in blood pressure, 
lipid levels, obesity, and other risk factors of 
cardiovascular disease. The Tokelu Island Mi- 
grant Study is an epidemiologically based in- 
vestigation of the changes in physical and socio- 
cultural environment that are associated with 
increased risk of cardiovascular disease, as 
Tokelauans migrate from their traditional atolls 
to New Zealand. The study is unique in that the 
population was surveyed before migration was 
completed in 1968 and both the nonmigrant 
population (in Tokelu) and the migrant population 
(in New Zealand) are subject to longitudinal 
followup. Migrants showed a considerable in- 
crease in the prevalence of hypertension and a 
less marked increase in mean blood pressure. 
Obesity, which is increased in the migrants, is 
clearly a factor in their elevated blood pressure. 



International Conferences, Seminars, 
and Meetings 

A conference titled "Nutrition and Blood 
Pressure Control: Current Status of Dietary 
Factors and Hypertension" was held in Septem- 
ber 1982. NHLBI staff chaired several sessions, 
and NHLBI grants and contracts supported the 
research of many of the speakers. The symposi- 
um provided a forum for communication among 
health professionals, biomedical investigators, 
and representatives of government and industry. 
Scientists from Canada, the Federal Republic of 
Germany, 3apan, the Netherlands, and the 
United Kingdom took part in the discussions. The 
role of sodium, potassium, divalent ions (calci- 



um, magnesium, selenium, and other trace ele- 
ments) on blood pressure was discussed. Other 
topics covered were the effects of macronutri- 
ents, alcohol, lipids, and carbohydrates on blood 
pressure and diet as opposed to drug therapy for 
hypertension. 

An international workshop, "Changing Patterns 
in Cardiovascular Disease in the Pacific Basin," 
was sponsored in January 1982 by the NHLBI in 
Kona, Hawaii. Areas represented were Australia, 
China, Fiji, Hawaii, Japan, Micronesia, Nauru, 
Niue, New Zealand, the Philippines, Rarotonga, 
Western Samoa, the United Kingdom, the United 
States, and Taiwan. Approximately 35 scientists 
and observers attended this workshop. Topics 
included stroke risk factors such as salt, blood 
pressure, and smoking; and demographic and 
socioeconomic factors of CHD, rheumatic fever 
and rheumatic heart disease, sudden death, and 
diabetes. The Pacific Basin region offers a 
unique opportunity to study how environmental 
and genetic factors interact to influence the risk 
of coronary heart disease, stroke, and hyperten- 
sion. Of particular interest is the comparison of 
cardiovascular risk due to patterns of migration. 

"Implications of Recent Beta-Blocker Trials 
for Post Myocardial Infarction (MI) Patients," a 
workshop held at the NHLBI in May 1982, 
reviewed and documented the state of knowledge 
regarding the effects of beta-blocking agents in 
post-MI patients to generate recommendations 
for future research on beta-blocking agents and 
to address questions regarding the implications 
of recent beta-blocker trials. Results from on- 
going long-term beta-blocker trials in Australia, 
the Federal Republic of Germany, the Nether- 
lands, Sweden, the United Kingdom, and the 
United States were compared. Experts from 
Ireland, Norway, Sweden, the United Kingdom, 
and the United States presented findings on the 
beneficial effects of administering these drugs 
following an acute heart attack. The U.S. par- 
ticipants presented the results of a randomized 
trial of propranolol in patients with acute MI. 
Thirty-six months following their acute MI, 
patients receiving propranolol had a survival rate 
significantly greater than that of a matched 
group of patients receiving a placebo. The Swe- 
dish workers reported similar favorable results 
with metoprolol, another beta-blocker. 



Intramural Programs and Activities 

Joint research was carried out in laboratories 
of the Division of Intramural Research, NHLBI, 
by 63 foreign investigators who came from Aus- 
tralia, Canada, China, the Federal Republic of 
Germany, France, Greece, Hong Kong, India, 
Ireland, Italy, Jamaica, Japan, Korea, Poland, 
Sweden, Turkey, the United Kingdom, and 
Taiwan. 



59 



The NHLBI intramural scientists and their 
French counterparts have been undertaking joint 
studies on the pathology of interstitial lung 
diseases (see France). These studies have proven 
valuable to both sides because they allowed 
pooling of scarce lung biopsy material from 
patients in both countries. 

Active research cooperation of NHLBI intra- 
mural scientists with their Japanese colleagues 
has taken place since 1966 (see Japan). This 
cooperative research is investigating the inter- 
relationship of nutrition, hypertension, and 



stroke; the researchers are using animal models 
of hypertension, stroke, and hyperlipidemia 
developed in Japan. These rat models of human 
disease have provided much new information on 
the basic etiology of these important diseases. 

A scientist from the Biochemical Pharmacol- 
ogy Section, NHLBI, conducted joint work in 
Australia to determine the role of the brain 
serotonergic system in the regulation of arterial 
blood pressure, and on techniques, including 
immunohistochemistry, applicable to the study 
of blood pressure. 



60 



Chapter VI 

National Institute of Arthritis, 
Diabetes, and Digestive and Kidney Diseases 



Introduction 

The National Institute of Arthritis, Diabetes, 
and Digestive and Kidney Diseases (NIADDK) 
conducts and supports biomedical research in a 
wide range of mostly chronic, often disabling, 
disorders. In many instances, these activities 
benefit from the contributions of members of 
the international scientific community. Contin- 
ued collaboration with international scientists, in 
addition to funding of research with the poten- 
tial for worldwide impact, remains an estab- 
lished priority for the Institute. 

Ongoing international programs of the Insti- 
tute are targeted at such areas as nutrition, 
arthritis, and thyroid hormone synthesis. 
Regarding international cooperation on nutrition, 
the Institute expects to increase an understand- 
ing of the influence of the environment on nu- 
tritional requirements; on the interaction of 
nutrition, immune competence, and infection; 
and on the health consequences of dietary pat- 
terns. In the area of arthritis collaboration, one 
goal is to ascertain the best drugs to treat 
juvenile rheumatoid arthritis. Cooperation in 
research into thyroid hormone synthesis might 
result in an improved treatment of hypo- 
thyroidism. 

Through international cooperation and col- 
laboration in areas such as these, scientists may 
perhaps control, prevent, and ultimately elimi- 
nate the many chronic and disabling disorders 
fcJling within the purview of the Institute. 

Summary of International Programs 
and Activities 

Bilateral Agreements and Other 
Country-to-Country Activities 

Through the Bilateral Cooperative Agreements 
Program, the NIADDK has developed collabo- 
rative and cooperative activities with France, 
Japan, and the U.S.S.R. These activities consist 
of the U.S.-3apan Malnutrition Panel Research 
Support Program, the U.S.-U.S.S.R. Cooperative 
Program in Arthritis, and the NIH-INSERM 
Agreement. 



The following discussion outlines the status, 
current activities, and accomplishments of the 
collaborative programs with the three nations. 



Japan 

The Malnutrition Panel, a binational steering 
committee of experts, was established in 1966 as 
part of the U.S. -Japan Cooperative Medical 
Sciences Program. The entire cooperative pro- 
gram, which covers a number of different dis- 
ease areas, is administered by the NIAID, but the 
malnutrition portion is the responsibility of the 
NIADDK Division of Digestive Diseases and 
Nutrition, with significant support from the 
NICHD. 

Malnutrition continues to be a serious problem 
in most Asian countries, the most common forms 
of which are protein-calorie malnutrition and 
deficiencies of iron and vitamin A. Also of con- 
cern are various disease states, particularly 
diarrheal infections, that impair the body's 
utilization of some nutrients or lead to the ex- 
cessive loss of others. These infections are the 
major cause of death in children under 5 years of 
age. Undernutrition also has a severely adverse 
effect on the outcome of pregnancy, increasing 
the number of infants born prematurely or with 
low birth weight and with more disabilities and 
inadequate nutritional reserves. Iron deficiency, 
a widespread disorder in Asia, causes anemia and 
all its attendant symptoms. It may also interfere 
with normal immune responses and may lower 
resistance to infection. Vitamin A deficiency is 
responsible each year for many thousands of 
cases of impaired vision and total blindness in 
children. 

The five priority areas of focus of the Malnu- 
trition Panel are: 

• Influence of environmental and host factors 
on nutritional requirements; 

• Health significance and methods of pre- 
venting iron deficiency; 

• Interaction of nutrition, immune compe- 
tence, and infection; 



61 



• Effects of nutrition on physical and mental 
development, behavior, physical capability, 
and work performance; and 

• Health consequences of different (and 
changing) dietary patterns and food habits. 

An announcement was made in FY 1982 
regarding the availability of grant support for 
studies on "Environmental and Host Factors 
Affecting Nutritional Requirements." In August 
1981, a workshop was held in San Diego, Cali- 
fornia, entitled "Opportunities for Collaborative 
Research Relating to Nutritional Requirements 
in Asian Countries." In attendance were nutrition 
scientists from Bangladesh, Burma, China, India, 
Japan, Malaysia, New Guinea, Thailand, the 
United Kingdom, and the United States. The U.S. 
Malnutrition Panel has also collaborated with the 
Japanese Malnutrition Panel to organize a work- 
shop, "Practical Approaches to Eradication of 
Subclinical Iron Deficiences," which was held in 
Tokyo on December 7 and 8, 1982. 

Recent findings from a number of nutrition 
research grants supported by the NIADDK and 
other NIH Institutes and identified as relevant to 
the U.S.-3apan program are listed below: 



Zinc — An important ongoing study at the 
University of Colorado has shown that low 
dietary zinc intake is a specific environmental 
factor that may contribute to poor linear growth 
velocity in children. This effect was observed in 
a double-blind controlled study of liO preschool 
children. Dietary zinc supplementation signif- 
icantly increased linear growth velocity in the 
boys, but not in the girls. 

Another study, at the University of Texas, 
suggests that a zinc-dependent enzyme, RNase, 
may be an appropriate means of monitoring zinc 
status in man. A group of young adult men were 
fed a zinc-deficient diet for 8 weeks, during 
which the activity of RNase was found to in- 
crease significantly in the parotid saliva and 
blood plasma during zinc depletion and return 
toward normal with zinc repletion. 

Iron .— In a study funded at the University of 
California at San Francisco, decreased red blood 
cell (RBC) survival in iron deficiency has been 
observed in association with increased RBC 
membrane stiffness. Decreased RBC deforma- 
bility in iron deficiency was shown to be due 
primarily to decreased membrane viscoelas- 
ticity. Iron-deficient RBC's showed increased 
susceptibility to peroxidation and showed evi- 
dence of spontaneous membrane lipid and protein 
cross-linking. These conditions suggest that 
increased RBC membrane stiffness in iron de- 
ficiency may be related to peroxide damage and 
is responsible for the observed decrease in RBC 
survival. 



In other studies on the effect of iron status on 
immunity in neonatal and maternal rats, results 
reveal that individual components of the immune 
response are affected differently by iron defi- 
ciency. While circulating immunoglobins (IgG or 
IqM) are resistant to change, the development of 
lymphoid organs such as the thymus and spleen is 
profoundly affected by iron deficiency, which 
may alter permanently the immunocompetence 
of the organism. 

Vitamin A .— At Tufts University, a rapid dark 
adaptation test has been developed that can be 
used under field conditions on children as young 
as age four. This method, which is very sensitive 
to vitamin A deficiency, involves matching the 
intensities of colored discs to the function of the 
cones in the eye (not rod function), so that under 
dim lighting conditions the ability to separate 
the different colored discs is dependent on rod 
function alone. This rapid dark adaptation test is 
expected to become widely used in surveys to 
identify subclinical vitamin A deficiencies. 

In other studies relating to vitamin A, two 
patients with markedly abnormal dark adapta- 
tion, despite normal serum vitamin A and zinc 
levels, experienced restoration of dark adapta- 
tion to normal through protein repletion alone 
(without supplemental vitamin A or zinc). These 
results argue that protein status does affect the 
ability of the retina to use vitamin A. 

Protein-Energy Requirements .— Studies are 
underway at Johns Hopkins University to assess 
the growth, body composition, and protein status 
of 6- to 36-month old infants on low, medium, or 
high levels of protein intake in relation to die- 
tary calories (from 4.7 to 8 percent calories 
from protein). So far, results have not identified 
significant differences in growth or body compo- 
sition because the numbers are too small for 
conclusive analysis. However, overall caloric 
intake appears to rise progressively as the per- 
cent of protein calories decreases. Also, changes 
in proportion between calculated arm muscle and 
fat cross-sectional areas favor the highest pro- 
tein intake group. 

At the Massachusetts Institute of Technology, 
noninvasive stable isotopes (^-^C, ^h, l^N) have 
been used to investigate the dynamic aspects of 
whole body amino acid metabolism in adult 
humans brought about by changes in intake of 
dietary protein and energy. Results, indicating 
that the synthesis of alanine is extensive and 
increases under conditions of low protein and 
high energy intake, suggest that alanine plays an 
important role in the retention and recycling of 
body nitrogen when there is a need to conserve 
nitrogen. In contrast, changes in glycine metab- 
olism do not appear to affect significantly the 
maintenance of the whole body nitrogen econo- 
my. In addition, this new technique is expected 
to be of value in determining the requirements 



62 



for essential dietary amino acids in human sub- 
jects. 

U.S.S.R. 

The U.S.-U.S.S.R. program of cooperation in 
arthritis originated with the Health Exchange 
Program of 1972, an agreement to improve col- 
laboration between the two countries in public 
health and medical service. In September 1973, 
arthritis became a subject of cooperation under 
this program. The program has three major 
divisions: clinical studies in rheumatic disease; 
studies in the basic science of rheumatic disease; 
and orthopedic surgery for arthritis, with em- 
phasis on clinical studies, using common, agreed- 
upon protocols for the treatment of rheumatoid 
arthritis and systemic lupus erythematosus. 

Over 100 subjects in both the United States 
and the U.S.S.R. are participating in an ongoing 
trial, begun in August 1981, of the comparative 
benefits of hydroxychloroquine and D-penicil- 
lamine in treating juvenile rheumatoid arthritis. 

Another study, at the University of California 
at Los Angeles, addresses the "Assessment of 
Methods for Measuring Hand Function in Rheu- 
matoid Arthritis." 

NIH-INSERM Agreement 

Under an agreement between the NIH and 
INSERM, substantial scientific collaboration has 
occurred between the Clinical Endocrinology 
Branch of NIADDK and the Unite de Recherche 
sur la Glande Thyroide et la Regulation Hormon- 
ale of INSERM. The exchange of scientists be- 
tween the two centers has provided excellent 
opportunities for collaborative research and the 
effective use of trained personnel in the study of 
thyroid hormone synthesis and metabolism. In- 
vestigators from both the United States and 
France have been working on separate but re- 
lated aspects of thyroid physiology and biochem- 
istry. Combining some of the resources available 
to each group has greatly enhanced the progress 
of research in these areas, and has led to the 
evolution of new procedures for solving problems 
of thyroid functions. 

In FY 1982, two French scientists engaged in 
collaborative research in a Clinical Endocrin- 
ology Branch laboratory. 



Extramural Programs 

To use the expertise available through bio- 
medical researchers in other countries and to 
further the progress of knowledge in high- 
priority health problems of international scope, 
the NIADDK continues to support projects ini- 
tiated by scientists located outside the United 
States who apply directly to the Institute's 
extramural research programs. In FY 1982, more 



than 30 such projects in the form of research 
grants, postdoctoral training grants, and coop- 
erative agreements were active at the NIADDK. 

International research funded by the NIADDK 
has made many contributions to knowledge, in 
both the clinical and basic science areas. For 
example, in the area of end-stage renal disease, 
work carried on at the University of Helsinki in 
Finland is attempting to describe the structure 
of inflammation in experimental and human 
kidney allograft rejection and to use these 
findings to develop new diagnostic methods for 
monitoring and counteracting rejection episodes 
in clinical transplantation. At the Karolinska 
Institutet in Sweden, the NIADDK is supporting 
prospective investigations into the metabolic 
effects of continuous ambulatory peritoneal 
dialysis. 

Some other current projects abroad relate to 
diabetes research. Research at Royal Southern 
Memorial Hospital in Australia is attempting to 
elucidate the genetic and environmental inter- 
actions that make for susceptibility to non- 
insulin-dependent diabetes mellitus (NIDDM). 
The objectives of the project are: (1) to deter- 
mine whether specific genetic markers exist in 
the NIDDM diabetic or in individuals with pre- 
disposing genes for diabetes; (2) to determine 
whether the differing susceptibility of various 
ethnic groups to NIDDM is related to the pres- 
ence or absence of these genetic markers; (3) to 
establish the relative roles of other factors such 
as age, nutrient intake, physical activity, obe- 
sity, and stress in the causation of NIDDM in 
genetically susceptible individuals; and (^) to 
identify possible preventive factors relating to 
NIDDM in high prevalence populations. The 
studies will be carried out in Caucasian, Mela- 
nesian, Polynesian, Micronesian, and American 
Indian populations. It is hoped that feasible in- 
tervention programs might be defined on the 
basis of future findings. 

A project at the Chaim Sheba Medical School 
in Tel Hashomer, Israel, is aimed at clarifying 
the risk factors for human glucose intolerance. 
The overall objectives are to quantify inter- 
relationships, distinguish between causes and 
effects, evaluate the relative role of environ- 
mental and genetic factors, and understand the 
temporal sequence of events among glucose 
intolerance, obesity, and macro- and microvas- 
cular complications of diabetes. 



International Conferences, Seminars, and Meetings 



Scientific meetings with an international 
audience play a major role in the interchange of 
biomedical information. They provide a forum 
for the exchange of research findings and in- 
formation among investigators from different 
countries, and they often stimulate further sci- 



63 



entific collaboration. The NIADDK continues to 
contribute toward the support of selected con- 
ferences within the United States and abroad, 
providing a setting for scientific cross-fertil- 
ization among international investigators. 

The International Society for Experimental 
Hematology (ISEH) held its eleventh annual 
meeting in Baltimore, Maryland, during August 
1982. The ISEH is a relatively young organiza- 
tion, which has grown to more than 500 members 
in the past 10 years. Meetings are held each 
year, alternating between the United States and 
foreign countries, usually in Europe. Topics 
presented at the Baltimore meeting included 
bone marrow transplantation, hematopoietic 
stem cell regulation, erthropoiesis, granulopoi- 
esis, lymphopoiesis, effect of radiation on stem 
cells, animal models for human hematopoietic 
disorders, and effects of aging on the hemato- 
poietic system. At past meetings of the ISEH, 
presentations have been made by scientists from 
such countries as Australia, Finland, the Federal 
Republic of Germany, Israel, the Netherlands, 
the United Kingdom, and Yugoslavia. As a focus 
for the initial presentation of work from labor- 
atories around the world, the annual meetings of 
the ISEH are an important mechanism of inter- 
national scientific exchange. 

The NIADDK provided major support for the 
Third International Congress on Nutrition and 
Metabolism in Renal Diseases, which was held in 
Marseilles, France, in September 1982. Previous 
congresses have been established to disseminate 
information about nutritional therapy to improve 
the metabolic and nutritional disorders associ- 
ated with chronic renal failure, both in patients 
who are not treated with dialysis and in those 
who are undergoing maintenance dialysis ther- 
apy. Knowledge in this area having expanded 
rapidly, the congresses have been designed so 
that clinicians and researchers pursuing basic 
and clinical investigations in various countries 
could meet and discuss areas of mutual interest 
and concern. The Organizing Committee of the 
Third Congress was composed of individuals from 
the United States, France, the Federal Republic 
of Germany, and Italy. Topics addressed included 
muscle and cellular metabolism in renal failure, 
catabolic stress in renal failure, endocrinemet- 
abolic disorders in acute and chronic renal 
failure, nutritional and metabolic aspects of 
continuous ambulatory peritoneal dialysis, con- 
servative management of chronic renal failure, 
techniques for prevention of progression of 
chronic renal failure, nutritional management of 
pediatric patients with renal failure, and the role 
of sodium and potassium intake in the etiology 
and management of hypertension. 

The Institute supported a colloquium entitled 
"Advances in Diabetes Epidemiology," which was 
held near Paris, France, in May 1982. Additional 
funding was provided by INSERM. The collo- 
quium was particularly timely because of recent 



efforts to establish uniform diagnostic criteria 
for diabetes. These criteria have been adopted 
by several organizations concerned with the 
disease. A second development that made the 
colloquium so relevant was the advent of popu- 
lation-based registries. The meeting was an 
attempt to pool data from all over the world in 
light of considerable new information on the role 
of viruses, autoimmunity factors, and histo- 
compatibility antigens in the etiology and path- 
ogenesis of diabetes. Also discussed were het- 
erogenicity in each of the types of diabetes, 
genetics, environmental etiologies of insulin- 
dependent diabetes, and studies of blood glucose 
levels in different groups and populations. 

The colloquium was held under the auspices of 
staff members of the Unite de Recherches Sta- 
tistiques and other French institutions. In addi- 
tion, there was a scientific committee composed 
of members from Australia, the Federal Repub- 
lic of Germany, and the United Kingdom, 

The NIADDK provided grants for a number of 
American scientists to attend the Twelfth In- 
ternational Congress in Perth, Australia, which 
was held in August 1982. Among the many topics 
covered were enzymology, enzyme mechanisms, 
protein synthesis, and the relationship between 
structure and function of biologically relevant 
molecules. Of high scientific quality, these tri- 
ennial congresses of biochemistry play an im- 
portant role in the progress of biochemical 
research throughout the world. 

Intramural Programs and Activities 

Intramural scientists at the NIADDK engage in 
a broad range of collaborative activities, both in 
foreign laboratories and with scientists from 
other countries who make use of the resources at 
the NIH. 

One program in which a number of intramural 
scientists participate is actually an initiative of 
governmental education authorities in Italy. It 
involves both travel to the NIH by young Italian 
scientists and corresponding visits to sponsoring 
Italian laboratories by NIADDK staff. 

At NIADDK, one laboratory carrying on col- 
laborative work under this program has been the 
Biochemistry of Cell Regulation Section in the 
Laboratory of Biochemical Pharmacology. 
Studies have been pursued on the structural 
properties of the receptor for thyroid stimula- 
ting hormone on normal thyroid plasma mem- 
branes, on plasma membranes of human and 
experimental thyroid tumors, and in strains of 
differentiated thyroid cells grown in vitro . These 
studies have established the role of glycoproteins 
and glycolipids in receptor recognition, the 
mechanism of message transmission, and the 
relevance of their functional expression in nor- 
mal and disease states such as goiter. Graves' 
disease, and hyperthyroidism. 



6k 



Research on vesicles coated with clathrin, a 
protein that provides a mechanism to bring thy- 
roglobulin and other substances into the cell, is 
being done by an NIADDK clinical endocrinol- 
ogist at the University of Naples. 

A Fogarty Scholar-in-Residence from Japan is 
one of the two or three preeminent scientists 
involved in the chemical synthesis of peptides 
and proteins. Thus far, he has spent about 6 
months in residence at the NIH, acting as a 
consultant to the Laboratory of Chemical Biol- 
ogy (LCB). He has been involved in work with 
NIH intramural scientists on the chemical syn- 
thesis of interferon and on the synthesis of pep- 
tides as inhibitors of the gelatin of sickle hemo- 
globin. During this time, the group synthesized 
and studied a number of peptides and tested 
their efficacy as gelatin inhibitors. 

Additional collaborative study of synthetic 
peptide inhibitors of sickle hemoglobin gelatin is 
ongoing between LCB scientists and a Nobel 
Laureate at the Medical Research Council Lab- 
oratory of Molecular Biology in Cambridge, 
England. Using synthetic peptides synthesized at 
the NIADDK lab, scientists are studying the 
binding of several synthetic peptides to crystals 
of hemoglobin to try to establish the mechanism 
of their gelation inhibition. Once this informa- 
tion is available, LCB scientists will design new 
and probably longer peptides, with the assistance 
of the molecular graphics system of the NIH 
Division of Computer Research and Technology. 

In a collaborative project with the Department 
of Morphology at the University of Geneva, 
Switzerland, the morphologic aspects of poly- 
peptide hormone interaction with target cells of 
insulin action, particularly in the liver, are being 
studied. These are the first studies to combine a 
biochemical approach and a physiologic approach 
with morphologic probes to demonstrate surface 
interactions and intracellular processing of 
polypeptides. 

Recent collaboration between the Nuclear 
Magnetic Resonance Section of the Laboratory 
of Chemical Physics and the Indian Institute of 
Science in Bangalore has centered on the basic 



molecular structure of peptides, using various 
methods of spectroscopy and X-ray diffraction. 

Another collaborative project involves the 
Laboratory of Biochemistry and Metabolism and 
the Weizmann Institute of Science in Rehovot, 
Israel. An effort is being made to map the 
three-dimensional structure of integral mem- 
brane proteins, using spectroscopic techniques. 
Integral membrane proteins, found in the phos- 
pholipid bilayer of cells, actually perform most 
of the active functions of the cell membrane. 
Researchers have collaborated to study, among 
others, bacterial rhodopsin, which is a unique 
pigment that permits bacteria to use light to 
generate energy (through the "proton pump" 
mechanism). The investigators believe that find- 
ing a way to inhibit the proton pump process may 
enable us to inhibit viral interaction with cells 
because the proton pump is always involved in 
such interactions. 



The NIH Visiting Program and Health Scientist 
Exchange Program 



Under the NIH Visiting Program, scientists at 
the NIADDK sponsor investigators from many 
countries to pursue work in laboratories on the 
NIH campus, and in turn many NIADDK re- 
searchers visit and collaborate in laboratories 
and clinics abroad. As the inevitable result of 
such a program, the cross-fertilization of ideas 
has mutual benefits for the United States and 
the foreign countries involved. Often it can lead 
to new advances in biomedical research. The 
following countries were represented in the 
Visiting Program during 1982: Australia, Austria, 
Bangladesh, Belgium, Canada, China, the Federal 
Republic of Germany, France, Ghana, Greece, 
Hungary, India, Israel, Italy, Japan, Korea, Mex- 
ico, the Netherlands, New Zealand, Nigeria, 
Pakistan, Poland, Portugal, the Republic of 
South Africa, Spain, Sweden, Switzerland, 
Trinidad, the United Kingdom, Yugoslavia, and 
Zimbabwe. 



65 



Chapter VH 
National Library of Medicine 



Introduction 

The international programs of the National 
Library of Medicine (NLM) are a natural exten- 
sion of NLM's domestic responsibilities. Coop- 
erative in nature, these activities have relevance 
to both the developed and the developing world. 

The advancement of biomedical and health 
research, education, and health care depends 
upon effective biomedical and health communi- 
cations. Through its activities, products, and 
services, the NLM fills the important role of 
coordinating biomedical and health information 
as it collects, organizes, and disseminates this 
information not only domestically but also glo- 
bally. The U.S. health professional benefits from 
the international character of the NLM collec- 
tion, its data bases, and its functions; the world 
health community derives benefit not only from 
NLM's products but also from NLM's inter- 
national collaborative undertakings. 

NLM's international activities fall into six 
general categories: literature exchange, library 
services. Special Foreign Currency (P.L. ^80) 
Program, MEDLARS cooperation, technical 
consultation, and participation in international 
organizations. Involving primarily a sharing of 
time, talent, and resources, these activities 
require a variety of mechanisms for execution, 
but all have a common objective: to benefit the 
U. S. health effort. 

Summary of International Programs 
and Activities 

Bilateral Agreements and Other 
Country-to-Country Activities 

International MEDLARS Agreement 

NLM's international MEDLARS quid pro quo 
arrangements have been in existence since the 
first arrangements with the United Kingdom and 
Sweden in 1 968. 

There is no transfer of monies between the 
participating country and the NLM. The NLM 
makes available the MEDLARS system, technical 
documentation, and training either through tapes 
or online access to the NLM computer. The 



participating country must meet technical cri- 
teria involving personnel, equipment, and fiscal 
resources and have a user community large 
enough to justify an extensive computerized 
service. The participating country then provides 
and/or funds the indexing of journal articles for 
input to the MEDLARS data base in return for 
access to the system. This practice is consistent 
with a policy adopted in 1966 by the Federal 
Council for Science and Technology, which was 
that Federal information systems would be made 
available in return for some contribution. 

The NLM does not select the institutions that 
will serve as MEDLARS Centers. The country 
itself makes that choice after meeting certain 
technical criteria established by the NLM. The 
MEDLARS Center may be in an organization 
primarily concerned with medicine or health, in 
a library, or within an organization broadly con- 
cerned with science and technology. In all cases, 
the foreign MEDLARS Centers function as a 
national biomedical information resource. 

A country has a choice of alternative 
MEDLARS arrangements: it may operate the 
system on its own computer using the NLM tapes 
(with or without NLM software) or it may use 
telecommunications linkages to access the NLM 
computer. Table 7-1 lists the regions, organi- 
zations, and modes of access. 

The Karolinska Institutet of Sweden hosted a 
meeting of policy officials from each of the 
countries with MEDLARS Centers. The meeting 
included a description from each of the officials 
about recent developments, plans for the future, 
quid pro quo arrangements, the role of govern- 
ment in providing biomedical information, the 
impact of technology, and the relationship 
between developed and developing countries. 

In their discussions of the role of the govern- 
ment, the members of the International 
MEDLARS Policy Advisory Group, which repre- 
sents health-related scientific and educational 
institutions and libraries in 12 countries, pre- 
pared a statement recognizing the NLM's lead- 
ership role and affirming that biomedical and 
health information is basic to maintaining and 
advancing biomedical and health research, edu- 
cation, and care. 

The Advisory Group's statement emphasizes 
the value of the MEDLARS system, referring to 
it as a national and international resource that 



66 



Table 7-1.— National Library of Medicine non-U.S. MEDLARS Centers 



Region 



Organization 



Mode of 
Access to 
MEDLARS 



Australia 
Canada 
Colombia 
France 



Germany (Federal 
Republic) 



Italy 

Japan 

Mexico 

South Africa 

Sweden 

Switzerland 

United Kingdom 

Intergovernmental 
Health 
Organization 



The National Library of Australia (NLA) Tapes/ 

Software 

Canada Institute for Scientific and Technical Information Online NLM 

National Research Council of Canada 

FUNDACION OFA and FONDO COLOMBIANO de Online NLM 

INVESTIGACIONES CIENTIFICAS (COLCIENCIAS) 

Institut National de la Sante et de la Online NLM 

Recherche Medicale (INSERM) 
Ministere de la Sante Publique et de la Securite Sociale 

Deutches Institut fur Medizinische Dokumentation Tapes 

und Information (DIMDI) 
Der Bundesminister fur Jugend, Familie und Gesundheit 

Istituto superiore di Sanita Online NLM 

Ministero della Sanita 

3apan Information Center of Science and Technology (3ICST) Tapes 
Science and Technology Agency 

Centro Nacional de Informacion y Documentacion en Salud Online NLM 

Ministerio de Salud 

Institute for Medical Literature Online NLM 

South African Medical Research Council 

Karolinska Institutet Tapes/ 

Software 

Schweizerische Akademie der Medizinischen Wissenschaften Tapes 

The British Library Online NLM 

Biblioteca Regional de Medicina (BIREME) Tapes/ 

Pan American Health Organization Software 



assists and enhances medical research, educa- 
tion, and health care delivery throughout the 
world. The statement describes the MEDLARS 
group of information services as an integral part 
of the research cycle and an important support 
to U.S. international relationships based on shar- 
ing knowledge, expertise, and facilities through 
bilateral arrangements. MEDLARS makes it 
possible to disseminate medical information 
efficiently and effectively to all countries, in- 
cluding those of the developing world. 



Special Foreign Currency Program 

The Library's Special Foreign Currency Pro- 
gram, authorized by P.L. 83-^80, as amended, 
relies upon appropriations of U.S.-owned, local 
foreign currencies to make awards for scientific 
writing and publication projects in cooperating 
countries, including Egypt, India, Israel, Paki- 
stan, Poland, and Yugoslavia. The programs in 
Israel and Poland were continued under collab- 
orative bilateral research agreements. 



67 



Projects in the six cooperating countries in- 
clude preparation of critical reviews and mono- 
graphs analyzing biomedical research and prac- 
tice; translations of foreign monographs in the 
health sciences; studies in the history of medi- 
cine; publication of major international symposia 
and conference proceedings; and preparation and 
publication of bibliographies, guides, and other 
literature tools in the biomedical sciences. The 
program enables the NLM to draw on foreign 
scientific personnel and resources in obtaining 
and disseminating information important to U.S. 
health educators, practitioners, and researchers. 

The projects are multiyear, and during FY 
1982 89 studies were active. Over 50 percent of 
the current program is carried out in Poland and 
Egypt, with about 20 percent in India. New crit- 
ical reviews and monographs in health fields 
constitute ^-5 percent of the projects, with 
projects concerned with the history of medicine 
representing another 30 percent. 

Among the new P.L. 480 projects activated in 
FY 1982 were a critical review on the endocrine 
system in patients with acute renal failure, 
publication in Egypt of the seventh volume of a 
major international bibliography of ticks and 
tickborne diseases, and translation of a Russian 
study of the geographical pathology of athero- 
sclerosis. Among the publications received in FY 
1982 resulting from prior support was a mono- 
graph entitled Chronic Hemodialysis as a Way of 
Life, written by two internationally renowned 
experts and addressed to medical and psychiatric 
practitioners. The book covers every aspect of 
hemodialysis. Another study recently published 
with support from the P.L. ^80 Program was an 
English language translation of the last work of 
the late Alexander R. Luria, a widely recognized 
Soviet neuropsychologist; the book, translated in 
India and printed in the United States, is called 
Language and Cognition. Among the recently 
published studies in the history of medicine was 
Two Great Scientists of the Nineteenth Century; 
Correspondence of Emil Du Bois-Reymond and 
Carl Ludwig. This book presents a 30-year cor- 
respondence between two of the most important 
figures in the development of modern physiology 
and offers an insight into 19th-century medicine. 
The text was translated in Tunisia and printed in 
India. 

Activities With Interaational Agencies 

World Health Organization 

The NLM and the WHO Special Program for 
Research and Training in Tropical Diseases con- 
tinued to cooperate in the publication of the 
Quarterly Bibliography of Major Tropical Dis - 
eases. The NLM prepares camera-ready copy 
that WHO prints and distributes to approxi- 
mately 5,500 institutions in the developing 
countries. The bibliography is prepared from the 



MEDLINE system and covers those diseases WHO 
had identified for special attention— filariasis, 
leishmaniasis, leprosy, malaria, schistosomiasis, 
and trypanosomiasis. 

Furthermore, the WHO Program for Control of 
Diarrheal Diseases requested NLM's assistance 
in a Bibliography of Acute Diarrheal Diseases 
which is planned for periodic publication. This 
bibliography has been issued for the first time 
within this fiscal year following the same pro- 
cedure of NLM's production of camera-ready 
copy from MEDLINE and WHO's printing and 
distribution. 

The NLM and WHO continued the collabora- 
tive arrangement for provision of photocopy of 
journal articles to developing countries of the 
WHO regions of Africa, Eastern Mediterranean, 
and Southeast Asia. Under this arrangement, 
WHO supports one individual in residence at the 
NLM to provide this service. This modest level 
of activity responds only partially to the existing 
biomedical and health information needs of 
developing countries. 

WHO has been actively working with devel- 
oping countries to identify existing resources for 
biomedical and health information and to de- 
velop mechanisms for providing information 
services. The Director of the National Library of 
Medicine is a member of the WHO Advisory 
Committee on Medical Research Subcommittee 
on Biomedical Information. Included in the sum- 
mary and recommendations of the final 1982 
report of the subcommittee was the following 
observation: 

Regional and national medical libraries and 
information networks to share scarce re- 
sources are now being planned or are under 
implementation or development in all regions 
in close contact with Headquarters. Those 
efforts are to be expanded and sustained as 
they are a prerequisite for the successful 
implementation of WHO health plans. The 
model of resource sharing and network im- 
plementation that is being developed by 
BIREME should be examined for its potential 
application in other areas of the world. 

The Subcommittee is pleased that several 
regions have or are preparing regional Index 
Medicus, that PAHO and Headquarters have 
developed document information services 
using the "Medical Subject Headings" (MeSH) 
vocabulary, and that SEARO and Headquarters 
are planning a pilot project for the biblio- 
graphic control of fugitive health literature on 
health services research. 

The Subcommittee recognizes that there 
exist national literature, documents, audio- 
visual materials, etc., which are not now ac- 
cessible in an organized manner.... Efforts to 
collect, organize and index such [fugitive] 
material into bibliographic systems should use 
the same internationally accepted cataloguing 



68 



rules and standards and MeSH, . . . resulting in 
bibliographic systems and products in the 
whole health field [which] will be compatible 
with each other and with the regional and 
global Index Medicus/MEDLARS. 

The Subcommittee considers the selective 
dissemination of bibliographic information 
with abstracts as exemplified by the Quarterly 
Bibliography of Major Tropical Diseases as an 
important and cost-effective method to keep 
health researchers in developing countries 
informed about progress in their field of in- 
terest. Access to full articles should be im- 
proved by resource sharing networks, regional 
interlibrary loans (photocopies) services and 
library manpower training. 

Pan American Health Organization 

The NLM continues to work with PAHO and 
especially with the PAHO Regional Library of 
Medicine (BIREME) in Sao Paulo, Brazil. 

The Library's Assistant Director for Interna- 
tional Programs, a member of the Scientific 
Advisory Committee for BIREME, will partici- 
pate in the 1983 meeting of this committee. 
BIREME is unique in the world as a regional 
resource. It provides library services and com- 
puter-based bibliographic services from the 
subset of the MEDLINE data base, trains Latin 
American librarians, and has produced a Latin 
American Index Medicus. 



International Council of Scientific Unions 
Abstracting Board 



The Assistant Director for International Pro- 
grams and the Deputy Director, as the NLM 
representative and alternate, respectively, to 
the International Council of Scientific Unions 
Abstracting Board, attended the annual meeting 
of the board. The board consists of information 
organizations from a number of countries. Topics 
discussed included collaborative undertakings, 
status of document delivery in various regions 
including the proposals of the Commission of the 
European Communities, working groups in vari- 
ous subjects, copyright, and an examination of 
the future role of the board in international, 
scientific, and technical activities. 



Visitors and Specialized Training 



The NLM continues to receive international 
visitors, as well as specialized delegations, who 
represented approximately S't countries during 
FY 1982. Formal delegations were concerned 
with international communications, library man- 
agement and resources, information systems 
management, and the impact of technology. 



69 



Chapter VHI 
National Institute on Aging 



Introduction 



By the end of the century, the total number of 
people in the world aged 60 and over will have 
doubled. Between 1975 and 2000, the number of 
aged in industrialized nations will increase 39 
percent; for developing countries, the increase in 
this population will be 100 percent. 

Although aging in itself is not a disease, the 
infirmities that accompany it must be examined 
and understood in order to extend the healthy 
and productive years, not simply to extend life 
itself. Although the relatively new fields of 
gerontology and geriatrics are developing rap- 
idly, substantive collaboration across borders and 
seas is just beginning to emerge. 

In May 1974, the United States National In- 
stitute on Aging (NIA) was created to support 
and conduct biomedical, social, and behavioral 
research and training related to the aging proc- 
ess and to the diseases and other special prob- 
lems of the aged. The Institute has extended its 
influence beyond national boundaries, demon- 
strating an interest in collaborating with the 
international scientific community and with 
multinational organizations, as reported in the 
sections that follow. 

Summary of International Programs 
and Activities 



Activities With the World Heahh Organization 

NIA's association with WHO began during the 
initial years of the Institute's existence. The 
relationship was formalized in 1980 when the 
NIA was designated as the first WHO Collabo- 
rating Center for Joint Cooperation on Research 
on the Care of the Aged. Over the years, the 
NIA Director and other staff members have 
served as advisors to the WHO Global Program 
on the Care of the Aged. During FY 1982, mem- 
bers of the Institute's staff have participated in 
a number of WHO-sponsored events. 

In October 1981, the NIA Director took part in 
a presentation titled "Research in Gerontology" 
before the WHO Global Advisory Committee on 
Medical Research (GACMR). On the basis of that 
meeting the committee recommended that a 
WHO group be convened to plan future cross- 



national epidemiological and social-survey re- 
search on the elderly and that a second WHO 
group be established to develop a program on 
senile dementia, because "a concentration of 
ideas, techniques, and research workers" now 
exists, as observed by the GACMR. The Group on 
Senile Dementia met in April 1982 and proposed 
seven areas of reseach for consideration: points 
of possible intervention in neurosynoptic trans- 
mission and neuropeptides; low viruses and pri- 
ons; genetic susceptibility; autoimmunity; trace 
metals; noninvasive studies of cerebral metabo- 
lism, including positron emission tomography; 
and neural membrane studies. The Institute will 
meet in January 1983. In both instances, the 
WHO Global Program on Care of the Aged is 
expected to develop worldwide networks of 
collaborating institutions. 

Also in connection with this meeting, the NIA 
updated an analysis of participating institutes 
and various national programs to provide a bet- 
ter understanding of their goals, priorities, or- 
ganizational structures, and activities. Overall, 
the analysis reveals that nations with widely 
differing political, cultural, economic, and social 
settings recognize the need for gerontologically 
related research and that this recognition often 
is in response to the growing number of older 
people in their own population. The WHO has 
viewed this effort as a basis for collegiate col- 
laboration between the institutes described in 
the profiles. The network is open-ended, and 
other institutes are welcome to take initiatives 
for research collaboration, either collectively 
with the network or individually with an insti- 
tute. Copies of "Profiles of National Research 
Institutes and Programs on Aging" are being 
transmitted by WHO to organizations concerned 
with aging listed in United Nations documents 
and by the International Federation on Aging to 
all its national member organizations. Interested 
individuals may obtain a copy from the Inter- 
national Coordinator, National Institute on 
Aging, Building 31, Room 2C07, National 
Institutes of Health, Bethesda, Maryland 20205. 

Extramural Programs 

The Institute's Biomedical Research and 
Clinical Medicine Program currently supports 
basic and clinical research through grants to five 



70 



investigators outside the United States (in Can- 
ada, Belgium, and Israel). Three of the projects 
deal with molecular and cellular biology, one 
with immunology, and one with the clinical path- 
ology of Alzheimer's disease. 

The project on Alzheimer's disease is being 
conducted by an investigator at the University of 
Western Ontario. It is designed to determine the 
relationship between pathological and clinical 
measurements of Alzheimer's disease using 
clinical, neurophysiological, biochemical, his- 
topathological, and radiographic characteristics 
of a well-defined clinical population. Results 
obtained during the first year of the grant in- 
dicate that viable synaptosomes (preparations of 
presynaptic nerve endings) suitable for neuro- 
chemical or neuropharmacological studies can be 
prepared if brain tissue is obtained within ap- 
proximately 8 hours after death. The synapto- 
somes will be used to provide data related to the 
disease process in patients afflicted with Al- 
zheimer's disease, particularly with regard to 
neurotransmitter function. 

Although the Behavioral Sciences Research 
Program of the Institute does not support in- 
vestigators from outside the United States di- 
rectly, it does support six domestic grants with 
foreign components. These are primarily cross- 
cultural and cross-national comparative studies 
related to such areas as aging and support sys- 
tems, community influence, retirement levels, 
and economic analyses involving specific popu- 
lations such as those found in Hong Kong, the 
U.S.S.R., Israel, and Eastern European countries. 



aging. Of the ^0 national reports submitted, the 
NIA provided the section on Research and Train- 
ing of the U.S. National Report. 

The developing countries' recognition that 
they will experience dramatic changes in age 
composition was a primary achievement of the 
assembly. The International Plan of Action calls 
for the Center for Social Development and Hu- 
manitarian Affairs in Vienna to serve as the U.N. 
focal point and coordinator for aging and to 
follow up on the objectives of the UNWAA. 

Other international workshops and conferences 
in which Institute staff participated during FY 
1982 are listed below. 

• WHO Workshop on Information Transfer 
in Mental Health 

• Planning Meeting for the WHO Confer- 
ence on Self-Care/Health Promotion 
Among the Elderly (to be held in 1983) 

• WHO Workshop on Health Planning for 
the Elderly 

• Special Meeting of the National Acade- 
my of Medicine of Mexico Concerning 
the Needs of the Elderly 

• International Congress on Aging and 
Environmental Factors 

• International Conference on Life-Course 
Research on Human Development 



International Conferences, Seminars, 
and Meetings 



• European Society of Neurochemistry 

• International Congress on Neuropathology 



The United Nations World Assembly on Aging 
(UNWAA) was held at the Hofberg Palace in 
Vienna, Austria, from July 26 to August 6, 1982. 
It was convened to address issues pertaining to 
worldwide population changes caused by declin- 
ing mortality, fertility, and migration. Numerous 
preparatory meetings, beginning as early as 
1979, were held around the world. 

The NIA contributed to the assembly in two 
capacities— as a member of the United States 
Federal Interagency Committee on Aging for the 
UNWAA and as a WHO collaborator. The NIA 
Director participated in the assembly as an 
advisor to the WHO delegation. WHO, as a 
specialized agency of the United Nations, pre- 
sented a "Technical Discussion Paper on the 
Health Policy Aspects of Aging," which was 
largely derived from the NIA-supported WHO 
Preparatory Conference for the UNWAA held in 
Mexico City in December 1980. 

Health and nutrition were dominant issues in 
the assembly's International Plan of Action, a 
plan that gives high priority to research on the 
developmental and humanitarian aspects of 



• Fifth International Symposium on Car- 
diology and Aging 

• Third International Erwin Riesch Sympo- 
sium on Cardiac Adaptation to Hemo- 
dynamic Overload Training and Stress 

• Tenth International Meeting of the In- 
ternational Society for Social Geron- 
tology 

• Chemical Institute of Canada's 65th 
Canadian Chemical Conference and 
Exhibition 

• Thirteenth Collegium Internationale 
Neuro-Psychopharmacologicum Congress 

• Meeting in France to Consult on Policies 
Concerning Research and Aging in France 

• WHO/Serono Symposia on Role of Basic 
and Applied Research in Achieving 
Health for All by the Year 2000 



71 



• International Conference on Aging of the 
Brain 

• Tenth Aharon Katz-Katchalsky Con- 
ference 

• Meeting with the WHO Collaborating 
Center on Health and Psychosocial 
Factors 

• International Symposium on the Aging 
Brain 



Intramural Programs and Activities 

The majority of the Institute's intramural 
research on aging is conducted at the Gerontol- 
ogy Research Center in Baltimore, Maryland. In 
FY 1982, information and research results were 
exchanged with visitors from 13 countries: Aus- 
tralia, Brazil, Canada, China, the Democratic 
Republic of Germany, France, the United King- 
dom, Italy, 3apan, Sweden, Switzerland, Thai- 
land, and Yugoslavia. 

The Human Performance Section of the Clin- 
ical Physiology Branch has two projects involving 
scientific exchange at the international level. 
Sample populations of normal Guamanians 
(Chamorros) and of Guamanians afflicted with 
amyotrophic lateral sclerosis/Parkinsonism de- 
mentia complex are utilized in collaboration 
with 3apan for cross-sectional and longitudinal 
evaluation of bone loss in a study related to 
osteoarthritis and bone loss, which are age- 
related changes of the human skeleton that may 
result in incapacity. 

The second study on normal human variance 
involves a continuing collaborative effort with 
WHO and other national and international bio- 
logical laboratories located in France, New 
Guinea, Greece, New Zealand, India, and Aus- 
tralia for the purpose of coordinating the col- 



lection, evaluation, and interpretation of der- 
matoglyphic data. The objectives of this project 
include the study of dermatoglyphics as it re- 
lates to aging, to distribution among human 
populations, and to genetics; and as it functions 
as a disease marker. 

Thus far, the study has revealed significant 
differences in the digital pattern frequencies of 
patients with breast cancer, individuals with high 
risk for developing breast cancer, and non- 
affected controls. 



NIH Visiting Program and Health Scientist 
Exchange Programs 

The NIA intramural program continues to 
enjoy active Visiting Program participation. 
During FY 1982, 3^^ scientists from 16 coun- 
tries—Australia, Canada, Chile, Egypt, Finland, 
France, Hungary, India, Israel, Italy, Japan, 
Poland, Sri Lanka, Sweden, Turkey, and the 
U.S.S.R.—received research training in the lab- 
oratories at the NIA Gerontology Research Cen- 
ter in Baltimore. 

The areas of research in which guest workers 
participated include pathophysiological and 
hormonal regulation of membrane transport 
systems; alteration of kidney membrane-bound 
enzymes in aging rats; studies on the relation- 
ships of cerebral metabolism to brain function 
and aging, the blood-brain barrier and central 
nervous system function, and transport systems 
active at the blood-brain barrier; drugs poten- 
tially useful for diseases prominent in sene- 
scence; the role of cell membrane structure on 
cellular recognition; a survey of the immune 
function of participants in the Baltimore Longi- 
tudinal Study of Aging; and learned modification 
of visceral function in man. In summary. Visiting 
Program participants contributed to 16 of 60 
NIA intramural projects. 



72 



Chapter IX 
National Institute of Allergy and Infectious Diseases 



Introduction 

The National Institute of Allergy and Infec- 
tious Diseases (NIAID) was formally established 
by law in 1948 as the National Microbiological 
Institute. Its name change in 1955 reflects a 
heightened emphasis on research in communi- 
cable diseases and immunological disorders. The 
NIAID assumed primary responsibility for ac- 
tivities in tropical medicine at the NIH in 1968 
when the NIH Office of International Research 
was disbanded. In 1979, the Office of Recombi- 
nant DNA Activities was assigned to the NIAID. 

Approximately 600 staff members at Bethes- 
da, Maryland, and at the Rocky Mountain facil- 
ities in Hamilton, Montana, carry out NIAID in- 
tramural research while the extramural research 
program is implemented through research or 
training grants and contracts awarded to aca- 
demic and research institutions. In FY 1982, 
tropical medicine and international research 
accounted for 73 percent of the extramural 
budget. 

In industrialized societies patients seek medi- 
cal attention for infectious diseases more fre- 
quently than for any other disorder. In develop- 
ing countries, these diseases are the leading 
cause of reported morbidity and mortality. Thus, 
advances in the domestic NIAID program have 
inherent and far-reaching relevance for national 
health authorities outside the United States and 
for agencies that cooperate with them in apply- 
ing new knowledge and technology to disease 
prevention and control. 

During FY 1982 the NIAID continued to assign 
special priority in its Tropical Medicine Program 
to filariasis, leishmaniasis, leprosy, malaria, 
schistosomiasis, and trypanosomiasis~the six 
diseases targeted for intensive research by the 
World Bank/UNDP/WHO Special Program for 
Research and Training in Tropical Disease 
(TDR). Priority placement on the six diseases 
also occurs through the NIAID International Co- 
operation in Infectious Diseases Research 
(ICIDR) Programs and through the Tropical Dis- 
ease Research Units (TDRU's). Research prog- 
ress on each of these tropical diseases is re- 
ported separately to facilitate communication 
and coordination with WHO and other interna- 
tional agencies that constitute a global network 
on research in tropical diseases. 



The NIAID Tropical Medicine Program also 
addresses other issues for which international 
collaboration is essential to complement the 
domestic research effort, including general 
parasitology; tropical bacteriology, mycology, 
and virology; rickettsioses; and vector patho- 
gens. Infectious diseases that constitute more 
serious public health problems in developing 
countries than in the United States are not in- 
cluded in NIAID's reporting of its Tropical Med- 
icine Program because the majority of these 
conditions are covered in NIAID domestic pro- 
grams. Examples include gastroenteritis other 
than cholera, hepatitis, acute respiratory ill- 
nesses, and sexually transmitted diseases. Thus, 
in addition to the NIAID Tropical Medicine Pro- 
gram, the bulk of which is carried out in the 
United States, this report also summarizes 
NIAID international activities in all disease 
areas. 

General parasitology consists of research on 
parasites of importance to human health other 
than those covered by the TDR Program. In- 
cluded are awards for basic research projects, 
parasitology research training, and career de- 
velopment awards that are not easily categor- 
ized specifically for any one of the targeted 
TDR diseases. The NIAID regards basic research 
in parasitology as a prerequisite to further ad- 
vancements in the prevention or control of all 
six parasitic diseases of TDR. Indeed, the PHS, 
Army, Navy, U.S. Agency for International De- 
velopment (US AID), and WHO disease-oriented 
initiatives have evolved from breakthroughs in 
basis research and will continue to rely on them 
to achieve their goals of vaccine and drug de- 
velopment or vector control. 

The rickettsial program, representing 6 per- 
cent of NIAID activity, is directed primarily 
toward Rocky Mountain spotted fever. Tropical 
bacteriology awards (7 percent) focus on cholera 
and related organisms, tuberculosis and myco- 
bacteria other than leprosy, and, to a lesser de- 
gree, spirochetes, plague, and yersinia. Although 
WHO has recently established a global Diarrheal 
Diseases Control Program with a major research 
component in epidemiology, improved drugs, and 
vaccine development, NIAID activities in viral 
and bacterial diarrheas (other than cholera), as 
indicated, are included in the regular program 
and hence are not part of the Tropical Medicine 
Program. Histoplasmosis and coccidioidomycosis 



73 



research (l.'f percent) constitutes the bulk of 
activities in tropical mycology. 

Tropical virology {7A percent) concentrates 
research projects on arboviruses, rabies, and 
other viral agents of public health importance 
(e.g., Lassa fever) that are not endemic to the 
United States. Vector pathogen activities (6.3 
percent), by contrast, consisted of 26 projects, 
10 on mosquito studies and others on tick, mite, 
and snail vectors of human viral, rickettsial, and 
trematode diseases. 

The three major categories of NIAID support 
for Tropical Medicine and International Health 
are intramural research, domestic extramural 
research, and competing foreign awards. Foreign 
investigators are eligible to compete with U.S. 
investigators for NIAID grants and, under special 
conditions, for contract funds. Most NIAID- 
sponsored international research, however, is 
generated through NIH awards to U.S.-based 
scientists and institutions. Approximately 70 
percent of the awards are for extramural grants 
or contracts to U.S. investigators or institutions. 
Awards to non-U. S. scientists or institutions 
represent 3 percent of the total Tropical Medi- 
cine and International Research budget. 

NIAID grants for ICIDR are intended to pro- 
vide linkages for research conducted outside the 
United States. The ICIDR Program, as well as 
the NIAID-supported Tropical Disease Research 
Units within the United States, is discussed in 
more detail under bilateral activities. Additional 
award mechanisms include bilateral medical re- 
search programs and the Special Foreign Cur- 
rency (P.L. i^ZO) Program, which involves six 
countries and is coordinated by the Fogarty In- 
ternational Center for the NIH. In FY 1982 the 
NIAID was most actively involved with Argen- 
tina, Australia, Brazil, China, Colombia, Costa 
Rica, the Dominican Republic, Egypt, France, 
Gambia, Ghana, India, Indonesia, Israel, 3apan, 
Kuwait, Mexico, the Netherlands, Nigeria, Pak- 
istan, Panama, Poland, Sierra Leone, Sudan, 
Sweden, Switzerland, Thailand, Trinidad and To- 
bago, the United Kingdom, and Venezuela. 

Going beyond the major award categories de- 
scribed above, the full extent of NIAID support 
for international health includes the overseas 
components of intramural or domestic extra- 
mural awards outside the diseases classified un- 
der the rubric of tropical medicine. 

Summary of Interaational Programs 
and Activities 



Bilateral Agreements and Other 
Country-to-Country Activities 

The NIAID conducts scientific exchange and 
collaborative research through a variety of 



mechanisms that extend from informal direct 
contact between investigators to formal agree- 
ments for cooperation between the United States 
and other governments. Because of its research 
responsibilities in tropical diseases, microbiol- 
ogy, and vaccine development, the NIAID has a 
particular need to foster cooperation with sci- 
entists and institutions in developing countries. 
In recent years, formal bilateral science and 
technology agreements with developing countries 
have proliferated, encouraging a tendency for 
these bilateral programs to move into additional 
areas such as immunology and genetic engi- 
neering. 

Argentina 

Long-standing collaboration with the Institute 
Fatala Chaban (Buenos Aires) on the cell biology 
of Trypanosoma cruzi strains and single cell 
isolate clones has been maintained. 

Australia 

Formal collaboration was begun between t'le 
NIAID and the Fairfield Hospital (Melbourne) on 
the biology of the hepatitis A virus. Collabora- 
tion was also initiated between the NIAID and 
the Australian National University. Research 
here will focus on the biology of mousepox virus 
and development of a simple, sensitive, and 
specific in vitro test for ectromelia virus to 
control and prevent this disease, which has re- 
cently produced epizootics at the NIH and rep- 
resents a serious threat to U.S. biomedical 
research. 

At present the NIAID extramural program 
supports five Australian investigators at the 
Walter and Eliza Hall Institute of Medical Re- 
search (Melbourne). In addition to ongoing sup- 
port for research on mechanisms of lymphocyte- 
antigen interactions, recent awards support the 
use of animal models for the development of 
vaccines against parasites, cell surface moni- 
toring by recirculating lymphocytes, investi- 
gation of T cell development in the thymus, and 
analysis of T hybrid mas with defined idiotypes. 

Bangladesh 

Collaborative research in Bangladesh has fo- 
cused on the Cholera Research Laboratory (CRL) 
in Dhaka. This productive relationship is chron- 
icled in Cholera; The American Scientific En - 
counter by Seal and van Heyningan, which will be 
published in early 1983. The NIAID collaborates 
with the International Center for Diarrheal 
Disease Research/Bangladesh (ICDDR/B) for 
longitudinal studies of viral gastroenteritis in 
infants and young children. (This research labor- 
atory was designated as the ICDDR/B in 1978 
and functions as a multilateral research insti- 
tute.) NIAID awardees in enteric diseases at 



7^ 



Harvard, 3ohns Hopkins, Maryland, and Wash- 
ington Universities continue to collaborate with 
ICDDR/B. In February 1982, NIAID staff visited 
ICDDR/B to identify additional areas for sci- 
entific exchange and collaboration. 

Belgium 

The NIAID continues collaboration with sev- 
eral Belgian scientists on the ontogeny and dif- 
ferentiation of cells of the rabbit immune sys- 
tem. The Director, Institut de Medicine Tropical 
(IMT) Prince Leopold (Antwerp), visited the 
NIAID early in 1982 to discuss development of a 
joint research effort directly between the NIAID 
and IMT, which would include joint activities in 
developing countries. 

Bolivia 

The NIAID is exploring the possibility of col- 
laborative activities in Chagas' disease and 
leishmaniasis with the Centro Nacional de En- 
fermedades Tropicales in Santa Cruz. Discus- 
sions were also held with the Institute of High 
Altitude Biology in La Paz on mutual interests 
related to effects of altitude and internal migra- 
tion on patterns of communicable diseases. 

Brazil 

Through a number of activities in Brazil, the 
NIAID has developed strong institutional ties. 
Efforts are now underway between the Fundacao 
Oswald© Cruz (FIOCRUZ) and the NIAID to de- 
velop a joint work plan in tropical medicine. 

In its intramural program, the NIAID has of- 
fered research training and bench facilities to 
Brazilian scientists for many years. Active col- 
laboration continues with scientists at the Uni- 
versity of Goias on the pathogenesis of leish- 
manial and T. cruzi infections. During FY 1982 
an NIAID Visiting Scientist spent 8 months at the 
University of Boias in cooperation with WHO to 
study Chagas' disease. Four of the 10 ICIDR 
awards made in FY 1982 to U.S. investigators 
are for collaborative studies in BraziL Cornell 
University Medical College collaborated with the 
University of Bahia on Chagas' disease and the 
endemic forms of cutaneous, mucocutaneous, 
and visceral leishmaniasis. The Harvard School 
of Public Health currently in its second ICIDR 
Program project, is collaborating with the Uni- 
versity of Bahia and FIOCRUZ in Rio de Janeiro 
on Chagas' disease and schistosomiasis. 

FIOCRUZ is also involved in a University of 
South Florida ICIDR exploratory grant on the 
spread of schistosomiasis in newly developed 
agricultural colonies in the northeast (Piaiu) and 
in settlement areas along the Trans-Amazon 
Highway. Columbia University participates in 
collaborative research with the Federal Univer- 
sity of Rio de Janeiro in which lectins are being 



used to study cell surface carbohydrates of viru- 
lent and avirulent forms of Leishmania . 

The Cornell on-site coordination for lab and 
field studies is based at the FIOCRUZ laboratory 
in Brotas, where major responsibility is building 
and maintaining a small animal colony. Most of 
the work at the FIOCRUZ is concerned with the 
immunology and biochemistry of leishmaniasis. 

At the Professor Edgard Santos Hospital, 
Bahia University investigators are exploring the 
genetics and clinical aspects of American vis- 
ceral leishmaniasis (AVL or kala-azar). Carefully 
designed, the genetic studies of AVL should yield 
definitive results on whether a genetic risk fac- 
tor is associated with AVL. The immune studies 
are concerned with lymphocyte transformation, 
suppressor cell concentration, and T helper and B 
cell activity. Also in process are field studies in 
Jacobina on AVL, a prospective longitudinal field 
study of AVL that has already provided new in- 
sights into the natural history of the disease, and 
studies of cutaneous and mucocutaneous leish- 
maniasis in Tres Bracos. 

At the Federal University of Bahia, the lab- 
oratory, which is managed by a Harvard immu- 
noparasitologist who established the ELISA test 
for serological identification of Chagas' disease, 
U.S. and Brazilian collaborators are hoping to 
develop an ELISA test for detecting circulating 
T. cruzi antigen to circumvent xenodiagnosis, a 
cumbersome and slow diagnostic technique that 
requires weeks instead of hours for results. Mon- 
oclonals and their corresponding antibodies de- 
veloped at Harvard will be used to identify 
strains of T. cruzi collected in different parts of 
Latin America. 

The Professor Edgard Santos Hospital, which 
houses a cardiology unit directed by the ICIDR's 
Brazilian collaborator, is engaged in a classical 
study of Chagas' cardiomyopathy. Field studies 
on Chagas' disease are planned and coordinated 
by a Brazilian epidemiologist trained at Harvard. 
Entomological studies stemming from colla- 
boration between the on-site coordinator and 
FIOCRUZ provide valuable information to con- 
trol units working in the study area. 

Canada 

NIAID scientists are collaborating with the 
University of Western Ontario on the genetic 
control and mapping of endogenous proviruses. 
During FY 1982, a new NIAID grant was awarded 
to the Montreal General Hospital for study of 
INR gene-complex probes in host-parasite inter- 
actions. A second award at the University of 
Manitoba concerns the suppression of the IgE 
response. 

China 

The U.S.-P.R.C. Joint Committee on Science 
and Technology in Medicine and Public Health 



75 



held its first meeting in Beijing in June 1979. 
The NIAID was assigned lead responsibility for 
immunology and secondary responsibility with 
the Centers for Disease Control (CDC) in para- 
sitology and infectious diseases. The parasitic 
and infectious diseases emphasized in the bilat- 
eral health protocol are malaria, schistosomiasis, 
hepatitis, and influenza. The NIAID subsequently 
assumed the lead role in recombinant DNA re- 
search within the Immunology Protocol. 

As a result of the exchange visits of the U.S. 
and Chinese coordinators, the protocol for co- 
operation in immunology was modified for FY 
1981-82 to include the immunology of infectious 
and parasitic diseases; cancer; diseases of the 
immune system, including primary immune defi- 
ciency diseases; autoimmunity and allergy; and 
skin and organ transplantation. The research 
approaches will involve immunobiology, immuno- 
genetics, molecular immunology, immunopharm- 
acology, and clinical immunology. The Immunol- 
ogy Work Plan provides for scientific exchange, 
research training, working groups, and collab- 
orative research in immunogenetics and clinical 
immunology. The U.S.-P.R.C. Joint Committee 
endorsed these modifications at its second meet- 
ing in the fall of 1982. The third meeting is 
scheduled for FY 1983 in Bethesda. 

By mutual consent, the highest priority in the 
Immunology Protocol is to enhance the research 
training opportunities for promising younger 
Chinese scientists at leading U.S. institutions. 
The Chinese Government, WHO, and private 
foundations have been very active in this area 
with U.S. universities outside the U.S.-P.R.C. 
Joint Committee and with minimal NIAID in- 
volvement. The Joint Committee has been an 
effective catalyst for research training and co- 
operative research at the NIH and other Federal 
agencies. In May 1982, U.S. scientists visited the 
University of Beijing and the Institute of Basic 
Medical Sciences, under the Immunology Proto- 
col. An NIAID scientist was one of three U.S. 
scientists who participated in a workshop, "Bio- 
chemistry of Schistosomiasis," in Shanghai in 
September 1982; an NIAID grantee at the Acad- 
emy of Natural Sciences (Philadelphia) traveled 
to China to study the distribution and ecology of 
snail vectors of schistosomiasis in Malaysia and 
Thailand. 

In FY 1982 NIAID signed a 2-year interagency 
agreement with CDC to share costs on a collab- 
orative protocol with the Institute of Virology 
(Beijing) and Shanghai First Medical College to 
study the efficacy of the NIH inactivated hepa- 
titis B antigen (HBsAg) carrier mothers. Vac- 
cines that were previously studied in Chinese 
adult volunteers are now being provided to in- 
fants born to HBsAg carrier mothers in Beijing 
and Shanghai. 

The NIAID also supported the participation of 
U.S. scientists in a workshop entitled "Origin of 
Pandemic Influenza Viruses." 



Colombia 

After 20 years of NIAID support for the In- 
ternational Center for Medical Research (ICMR) 
in Call, scientists at Tulane University have 
proposed collaborative research with the Colom- 
bian Fund for Research (COLCIENCIAS) under 
the ICIDR mechanism. Now in its second year, 
the research emphasizes both epidemiological 
and basic biological investigations of selected 
vector-borne diseases, especially filariasis and 
trypanosomiasis. The ELISA test is being used 
for serological testing of patients from endemic 
areas with W. bancrofti . Strains of T. cruzi and 
T. rangeli have been cloned and will be reeval- 
uated biologically and for isoenzyme characters 
prior to large-scale production of stage-specific 
antigens. 

As the Tulane-COLCIENCIAS ICIDR builds on 
long-standing ICMR collaboration, joint publi- 
cations in refereed journals are already begin- 
ning to appear. Field studies along the Colom- 
bian bank of the Amazon demonstrated an 
average prevalence of mansonellosis in teen- 
aged and adult Amerindians of ^7 percent (range 
16-85 percent). Entomological studies confirmed 
studies in Brazil that Simulium amazonicum and 
S. argentiscutum serve as intermediate vectors 
and confirmed conclusively for the first time in 
South America that culicine mosquitoes ( C. 
insinuatus) can serve as vectors. Similar studies 
confirmed the presence of Dipetalonema pers - 
tans in the Colombian Amazon (Guainia) and that 
its prevalence (10.6 percent) and distribution 
may be far greater than previously suspected. 



Costa Rica 

For 7 years, the NIAID has supported epidem- 
iological studies of viral hepatitis by U.S. and 
Costa Rican scientists associated with Louisiana 
State University. In FY 1982, the team reported 
on a prospective investigation of the spread of 
hepatitis A virus (HAV) within households in two 
rural areas in Costa Rica. The initial prevalence 
of anti-HAV antibody was 26 percent in children 
and 71 percent in adults. Overall, 70-83 percent 
of antibody negative contacts acquired HAV in- 
fection. In contrast to observations in the United 
States, almost all "susceptible" adults developed 
inapparent infection while the clinical/silent 
case ratio in children was 1.8/1. The absence of 
IgM in older people suggests that antibody con- 
version in many Costa Rican adults represents 
reinfection and restimulation of IgG rather than 
new disease. 

Denmark 

In October 1981, the Deputy Director General 
of the National Board of Health visited the 
NIAID. 



76 



Dominican Republic 



Finland 



The University of Arizona collaborative 
studies between the NIAID and the Instituto 
Dermatologico (Santo Domingo) continue. The 
studies are significant because this focus on 
leishmaniasis in the Dominican Republic is the 
only documented concentrated attention on this 
disease in the Caribbean proper. This study has 
demonstrated a uniquely high incidence of dif- 
fuse cutaneous leishmaniasis, a rare manifesta- 
tion previously reported in Ethiopia and Vene- 
zuela. 

The University of South Florida is supported 
through the NIAID regular grants program to 
study filariasis in the Dominican Republic. 

Ecuador 

In April 1982, the Chief, National Planning 
Division, Ministry of Public Health, visited the 
NIAID under the auspices of the Eisenhower Ex- 
change Fellowship Program. 



Egypt 

The NIAID has been involved in collaborative 
research with Egyptian investigators for more 
than a decade, most recently under the terms of 
the U.S.-Egypt Agreement for Collaboration in 
the Areas of Science and Technology. Collab- 
orative projects funded by the Special Foreign 
Currency (P.L. li&O) Program were the following: 
(I) Taxonomy of Genus Bulinus, (2) Bionomics of 
Anopheline Vectors of Malaria, (3) Ticks and 
Tickborne Diseases of the World, and W Epi- 
demiology of Bancroftian Filariasis. 

The NIAID is involved in collaborative efforts 
with CDC-administered P.L. 480 projects. The 
Laboratory of Infectious Diseases and the 
NIAID-funded Infectious Enteric Diseases Study 
Center at the University of Texas (Houston) 
provide virologic and bacterial support respec- 
tively to the Diarrheal Diseases Project at the 
Epidemiology Study Center in Bilbais. 

The NIAID contract with the Research and 
Training Center on Vectors of Disease (Ain 
Shams University) to produce a study entitled 
"Epidemiology and Control of Vector-Borne 
Diseases in Egypt," a USAID-funded project ad- 
ministered by the NIAID, began in December 
1981. Cooperating Egyptian institutions in FY 
1982 included the Ministries of Health and 
Agriculture; El Azhar, Canal, and Cairo Univer- 
sities; and the High Institute of Public Health 
(Alexandria). Participating U.S. institutions in- 
cluded NAMRU-3, Walter Reed Army Institute 
of Research, CDC, Cornell, Harvard, Michigan 
State, and Yale. The first year activities con- 
centrated heavily on the development of re- 
search projects in Rift Valley fever, leishmani- 
asis, malaria, and medical entomology. 



In FY 1982 the NIAID extended its contract 
with the Central Public Health Laboratory to 
provide foUowup studies of children immunized 
with meningococcal type A vaccine from 197'f to 
1978. The original contract resulted from a 1973 
request from the Finnish National Board of 
Health for assistance in dealing with an epidemic 
of that disease. The new contract includes eval- 
uation of the response to Hemophilus influenza , 
type B vaccine administered as a control in the 
197^^ efficacy trials. The recently signed Memo- 
randum of Understanding between the DHHS and 
the Ministry of Social Affairs and Health pro- 
vides for the development and testing of vac- 
cines. The DHHS has proposed that the director 
of the NIAID Microbiology and Infectious Dis- 
eases Program serve as the U.S. coordinator in 
this program area. 

France 

During FY 1982 the NIAID continued its 21 
years of support to a Nobel laureate for his work 
on skin grafts and surface leukocyte antigens. 
The Institut Pasteur began work on a new NIAID 
grant to study mechanisms of antigenic variation 
in T. equiperdum . NIAID intramural scientists 
also collaborated with this institute on genetic 
studies of immunoglobulins and other serum 
proteins, with the CNRS on the structure and 
activity of immunologically important cells and 
proteins, and with the Faculty of Medicine/Brest 
on tickborne disease agents. In FY 1982 the 
NIAID initiated collaborative work for basic 
studies on mycoplasmas and related wall-free 
prokaryocytes. Collaboration was also begun 
with the Hospital Cochin (Paris) on the structure 
and function of endogenous murine C type viral 
products. In September 1982, the Director, 
NIAID, visited INSERM and the Institut Pasteur 
to discuss opportunities for more extended 
Franco-American collaboration in immunology, 
microbiology, epidemiology, and clinical in- 
vestigation. 

Gambia 

The NIAID and NCI initiated discussions this 
year with the Medical Research Laboratories 
(Banjul) on the feasibility of cooperative epi- 
demiologic studies on the efficacy of hepatitis B 
vaccine in preventing disease, duration of im- 
munity, and prevention of hepato cellular car- 
cinoma. NIAID intramural scientists and New 
York University staff spent several weeks in 
Gambia under USAID and WHO support to con- 
duct field trials on the application of radio- 
immunoassay, using hybridomas to P. falciparum 
in the determination of sporozoite infection 
rates in Anopheles gambiae mosquitoes, a sig- 
nificant development in malaria research. 



77 



Democratic Republic of Germany 

A new intramural project was initiated in 
collaboration with the Academy of Science 
(3ena) on the molecular and genetic analysis of 
plasmid-mediated properties among streptococci. 



Federal Republic of Germany 

Collaboration between the NIAID and the 
University of Munich on the systemics and vec- 
tor relationships of parasitic arthropods con- 
tinued. Grant support was also provided to the 
Max Planck Institute for Biology on the poly- 
morphism of the major histocompatibility com- 
plex. 

Ghana 

During FY 1982, NIAID intramural staff made 
a short trip to the Onchocerciasis Hospital in 
Tamale, supported through P.L. 480 funds. A 
protocol was developed and arrangements made 
for a hospital researcher and an NIAID medical 
staff fellow to collaborate in Ghana under a TDR 
grant to initiate clinical and immunologic studies 
of the reactions (Mazzotti) that occur after 
treatment of patients with diethylcarbamazine. 

Haiti 

The Tulane ICIDR Program continues its col- 
laborative project on the epidemiology of filarial 
infection in Haiti, with the Institut Francais 
d'Haiti. In November 1981 the Association of 
Medical Microbiology Chairmen met in Port-au- 
Prince, providing NIAID senior staff an oppor- 
tunity to meet with USAID country health staff. 



India 

Since 1962 the NIAID has participated in col- 
laborative research with Indian investigators, 
largely through P.L. ^^80 Program funding. In 
December 1981 the Indian-U.S. Working Group 
on Health of the 3oint Science and Technology 
Committee met in New Delhi to review and re- 
define priority diseases for collaborative re- 
search. Mutually agreed-upon areas for emphasis 
were acute respiratory diseases, diarrheal dis- 
eases, filariasis, guinea worm, hepatitis, Japan- 
ese encephalitis, leprosy, malaria, recombinant 
DNA technology, rheumatic fever and sequelae, 
and tuberculosis. The NIAID reviewed the status 
of these activities with the Indian Council of 
Medical Research staff in New Delhi in March 
1982 and in Washington later in the year with the 
Secretary of the Ministry of Health and Family 
Welfare. 

In 3uly 1982 President Reagan and Prime 
Minister Gandhi met in Washington and agreed to 



establish a Joint Indo-U.S. Senior Scientific 
Panel to consider research areas of priority to 
both countries. Biomedical research on leprosy, 
immunology, and prevention of blindness were 
identified as the three program areas in health. 
This initiative will begin in FY 1983. 

A new area of cooperation to which the ICMR 
gives high priority is acute respiratory diseases, 
which are major causes of morbidity and mor- 
tality in Indian children. 

Collaboration continues among the NIAID, the 
Tuberculosis Research Center (Madras), and the 
Madras Medical College on the immunology of 
filarial infections and the pathogenesis of tro- 
pical eosinophilia and lymphangiitis. Current 
studies under the project include (1) evaluation 
of the pathogenetic significance of blocking an- 
tibodies that regulate immediate hypersensi- 
tivity responses in patients with filariasis, (2) 
determination of the mechanisms responsible for 
the control of allergic responses to the parasite, 
(3) comparison of the IgE regulatory mechanisms 
in patients with filariasis and other allergic 
disorders, (4) definition of the IgE as opposed to 
the IgG response of patients with filariasis to 
other specific antigens, (5) production of mono- 
clonal antibodies to filarial antigens for use in 
the development of immunodiagnostic or pro- 
tective immune reagents and, (6) chemothera- 
peutic studies of optimal drug regimens for this 
difficult-to-manage disease. 

The NIAID continues collaborative studies at 
the National Institute of Virology (Poona) on the 
epidemiology of hepatitis in India. With the ap- 
plication of recently developed laboratory tests, 
it is now apparent that the 1955-56 massive 
water-associated outbreak of hepatitis in Delhi 
was neither hepatitis A nor B. Ongoing studies 
indicate that non-A, non-B hepatitis is a com- 
mon source of epidemic and sporadic hepatitis in 
India. NIAID experiments at the NIH have pro- 
duced hepatitis in chimpanzees following the 
inoculation of infectious Indian material but 
have not yet recovered and characterized the 
etiologic agent. As epidemic non-A, non-B hep- 
atitis is particularly severe during pregnancy, 
efforts are now underway to develop a study 
with the National Institute of Virology on the 
epidemiology of hepatitis of pregnancy and 
childhood cirrhosis. During FY 1982 collabora- 
tion was extended to include the Postgraduate 
Institute of Medical Education and Research 
(Chandigarh) and investigators in Srinigar. 

Agreement to undertake a new area of coop- 
eration—in Japanese encephalitis—was reached 
in FY 1982. In 1981 the Government of India 
made a policy commitment to eliminate leprosy 
as a public health problem by the end of the 
century. Indo-U.S. collaboration in leprosy has 
been shared within the PHS among the National 
Center for Hansen's Disease in Carville, Louis- 
iana; NIAID; and CDC. The Central Jalma In- 
stitute for Leprosy (Agra) was awarded one of 



78 



the first two ITDR Fellows for a year of re- 
search training in mycobacteria at the Tubercu- 
losis Research Center of the Veterans Admini- 
stration Medical Center (Long Beach). Approval 
was confirmed for a collaborative P.L. ^&0 
project between scientists of Johns Hopkins 
University and the Foundation for Medical 
Research (Bombay) on the screening of drugs for 
activity against leprosy and the detection of 
drug resistance. 

The University of Hawaii has an ICIDR ex- 
ploratory award to collaborate with the Aligarh 
Muslim University on the in vitro cultivation of 
human malarial parasites isolated in India, the 
drug susceptibility of Plasmodium falciparum , 
and the culture of Indian P. vivax strains in 
vitro . NIAID intramural scientists visited the 
Central Drug Research Institute (Lucknow), and 
two collaborative protocols were completed: 
"The identification of immunogens and immuno- 
suppressive molecules in primate malarias" and 
"Studies on immunity to the sexual stages of the 
malarial parasite." 

Plans for a fixed-site Indo-U.S. Workshop on 
Recombinant DNA were modified in favor of a 
March visit by a team of four U.S. scientists led 
by the Deputy Director of the NIAID. The team 
became familiar with leading Indian scientists 
and institutions active in this area. Further 
activities and followup are expected to be in- 
corporated into the new Indo-U.S. Senior Sci- 
entific Panel. 

In rheumatic fever and streptococcal disease, 
efforts are underway between the University of 
Tennessee and the ICMR Streptococcal Typing 
Center (New Delhi) to study the epidemiology of 
group M streptococcal protein in India. 

A collaborative project with the All India In- 
stitute of Medical Sciences (AIIMS) to adapt the 
radioimmunoassay (RIA) technique to the de- 
tection of secretory tuberculoprotein has been 
developed by two scientists (one, a Nobel laur- 
eate) at the Montefiore Medical Center (New 
York City). If successful, this effort should fa- 
cilitate the definitive diagnosis of primary cen- 
tral nervous system and other extrapulmonary 
forms of tuberculosis within days rather than the 
weeks now required for the culture and identi- 
fication of Mycobacterium tuberculosis . The 
AIIMS is also in a position to apply the RIA tech- 
nique to other health problems and to serve as a 
national center in this field. 

Indonesia 

Representatives of the National Institute for 
Health Research and Development (NIHRD) 
visited the NIAID in November 1981 to become 
familiar with the NIH. In September 1982 an 
NIAID scientist made a short site visit to the 
USAID-supported Health Training, Research, and 
Development Project to examine the biomedical 
research subproject of the NIHRD. 



Israel 

The NIAID contract with the Kuvin Center for 
the Study of Infectious and Parasitic Diseases 
(Hebrew University) on the "Epidemiology and 
Control of Vector-Borne Diseases in Israel" be- 
gan operations in December 1981. This USAID- 
funded project involves significant collaboration 
in medical entomology with Beersheva Univer- 
sity of the Negev and focuses heavily on leish- 
maniasis research and field studies and on sur- 
veillance for leishmaniasis. Rift Valley fever, 
and malaria. 

During FY 1982 the NIAID supported three 
ongoing investigator-initiated grant awards at 
the Weizmann Institute for research on bioener- 
getics and control of bacterial behavior at Ha- 
dassah University Hospital on new approaches to 
marrow and organ transplantation and at the 
Israel Institute of Technology on the differen- 
tiation and activity of mast cells in culture. Ac- 
tive collaboration exists between the NIAID and 
the Hadassah Medical Center on the character- 
ization of surface IgG in the clones of a murine 
B cell lymphoma. 

Italy 

A transmissable hepatitis agent, the delta 
agent appears to be defective in that it requires 
coinfection with hepatitis B virus for its own 
synthesis. The delta agent is endemic in Italy 
where it was discovered in 1977. An NIAID sci- 
entist is collaborating with Italian investigators 
on this unique virological phenomenon. A sci- 
entist in Rome also continues his collaboration 
with the NIAID on rabbit IgG allotypes. 



Japan 

The NIAID is currently involved in two Japan- 
U.S. initiatives. The first is the U.S.- Japan Co- 
operative Medical Science Program (JCMSP), 
initiated in January 1965. Under the terms of 
this agreement, both countries have undertaken 
joint cooperative biomedical research in diseases 
of particular importance in Asia. Under P.L. 86- 
610 (the International Health Research Act of 
1960) the State Department coordinates foreign 
relations and policy of the program while DHHS 
is responsible for the scientific elements. The 
NIAID has been the lead institute within the NIH 
and DHHS since 1968. Although the JCMSP 
operates as a bilateral program, scientists from 
other countries and/or international agencies 
often participate. Applications submitted within 
the context of this program by U.S. scientists 
compete for available funds on the basis of their 
scientific merit without a special NIAID budget 
set-aside. Japanese scientists, in contrast, 
depend on the program to facilitate their funding 
proposals. 



79 



Currently there are eight panels: leprosy, 
tuberculosis, cholera, hepatitis, parasitic dis- 
eases (schistosomiasis and filariasis), viral dis- 
eases (arboviruses, rabies, rotaviruses), environ- 
mental mutagenesis and carcinogenesis, and 
malnutrition. These panels meet annually either 
in the United States or Japan. The Director, 
NIAID, and staff members serve as the Secre- 
tariat to the U.S. delegation to the 3CMSP and 
to six of the panels. 

At the 1982 3CMSP Joint Committee meeting 
in Tokyo, the formal review of the Leprosy and 
Parasitic Diseases Panels was completed, and 
the Tuberculosis and Viral Diseases Panels were 
initiated. The committee recommended that the 
Leprosy and Parasitic Diseases Panels be con- 
tinued and held additional discussions of the 
Leprosy, Tuberculosis, and Parasitic Diseases 
Panels. Recognizing the common scientific in- 
terests of the Leprosy and Tuberculosis Panels, 
the committee recommended that these two 
panels hold combined meetings beginning in FY 
198^. The committee agreed also that the guide- 
lines of the Parasitic Diseases Panel should be 
reviewed to accommodate new technologies and 
changing needs. Preparatory to such action, a 
symposium will be held in conjunction with the 
July 1983 Joint Committee Meeting in Bethesda. 
Experts will be invited to present current sci- 
entific reviews for such parasitic diseases as 
malaria, leishmaniasis, and trypanosomiasis, in 
addition to schistosomiasis and filariasis. 

The second U.S. -Japan initiative developed 
when the President of the United States and the 
Prime Minister of Japan signed the Japan-U.S. 
Science and Technology Agreement for Non- 
Energy Cooperation in May 1980. This agreement 
is separate from, but coordinated with, the 
JCMSP. Within this second bilateral program the 
NIAID has lead responsibility for three program 
areas: immunization (vaccine development), re- 
combinant DNA research, and antiviral agents. 
At the first meeting of the U.S.- Japan Program 
for Cooperation in Science and Technology 
(Tokyo, September 1981), both countries agreed 
to continue to develop recombinant DNA re- 
search activities within the "umbrella" Science 
and Technology Program. The technical aspects 
of vaccine development and antiviral agents, 
however, will remain with the appropriate 
JCMSP Panel, with the referral of matters 
requiring policy review and decisions to the U.S. 
Chairman of the Science and Technology 
Program. 

JCMSP panel meetings during FY 1982 in- 
cluded the following: cholera, virology, hepatitis, 
immunology, tuberculosis, leprosy, and parasi- 
tology. Meetings held under the auspices of the 
U.S.- Japan Non-Energy Science and Technology 
Program were limited to a symposium entitled 
"The Introduction of DNA into Eukaryocytic 
Cells" and a meeting of the Recombinant DNA 
Panel. 



Outside the two formal bilateral programs, 
two NIAID intramural laboratories have ongoing 
collaboration with Japanese scientists. One is 
actively involved with the University of Tokyo in 
the fractionation of lymphoid cell subsets with 
lectins that specifically bind to cell surface 
glycan differentation markers. The other, the 
Rocky Mountain facilities, also maintains col- 
laboration with scientists at the National In- 
stitutes of Health (Tokyo) on tickborne disease 
agents. In addition, the NIAID supports one ex- 
tramural award at St. Marianna University on 
genetic studies in the Aedes (Finlaya) toRoi 
mosquito. 

Kenya 

During FY 1982 the NIAID initiated a domes- 
tic grant to Cornell University to study the 
longitudinal effect of treatment of Schistasoma 
hematobium on the nutritional status of school 
children. Parameters to be followed include 
physical fitness and urinary excretion of iron. 

Kuwait 

The Director of the Immunology, Allergic and 
Immunologic Diseases Program (lAIDP) continues 
to serve as a consultant to the Ministry of Public 
Health in the development of a national allergic 
disease program and the construction of an al- 
lergy research center. 

Mexico 

The University of Washington has an explor- 
atory ICIDR award for work with the National 
Polytechnic Institute (Mexico City) on the ser- 
odiagnosis of subclinical leprosy. During the past 
year the surface protein of live M. leprae has 
been found to consist of five major subunits. A 
36,000 dalton subunit common to M. leprae , M. 
leprae murium, and BCG may represent a shared 
antigen. The NIAID continues association and 
collaborative research that began over 10 years 
ago with Mexican scientists and the Center for 
the Study of Amebiasis (Mexico City). The NIAID 
also provided support for U.S. scientists to at- 
tend an International Symposium on Immunobi- 
ology of Infectious Disease. Approximately 200 
Mexican immunologists participated in the sym- 
posium. The PHS subsequently convened a meet- 
ing at the NIAID to discuss cooperation between 
the United States and Mexico on research and 
training in communicable diseases. Economic 
conditions in Mexico, however, limited followup. 

Netherlands 

Two intramural laboratories have continuing 
collaborative research activities with counter- 
parts in the Netherlands: one with the Nether- 
lands Red Cross Book Transfusion Service on the 



80 



mechanisms of immune recognition of viral an- 
tigens and the other with the Catholic University 
of the Netherlands on the taxonomy, ecology, 
and colonization of parasitic arthropods of med- 
ical importance. Two research contracts with 
the University of Leiden are concerned with the 
acquisition of homozygous typing cells and anti- 
sera to HLA-A,B, and C loci and b cells. 

Nigeria 

Ohio State University has an active ICIDR 
exploratory grant with the University of Nsukka 
to study the biological control of mosquitoes 
that transmit malaria by Bacillus thuringenesis . 
A Nigerian Visiting Fellow at the NIAID is car- 
rying out investigations on the binding of red 
blood cells infected with malaria to the endo- 
thelium of blood vessels. The NIAID also par- 
ticipated actively in the biomedical research 
component of the U.S.-Nigeria Joint Task Force 
on Health Cooperation. 

Pakistan 

Although the University of Maryland Inter- 
national Center for Medical Research at the 
Pakistan Medical Research Center (Lahore) 
terminated in May 1980, the NIAID maintains an 
active project with the University of Maryland 
on the ecology of mosquitoes in Pakistan and the 
genetic control of Anopheles culicifacies , an 
important vector of malaria in that country. 

Panama 



Humboldt Institute") of the Universidad Peruana 
Cayetano Heredia, as the national research 
center for infectious and tropical diseases. The 
NIAID maintains regular contact with the 
institute. 

Poland 

In October 1981 the Chairman of the Coordi- 
nating Commission for Polish-American Scien- 
tific Collaboration visited the NIAID to discuss 
active projects in the Polish-U.S. Agreement on 
Cooperation in the Field of Health. At present 
there are two active projects with extramural 
scientists on the immunochemistry of Shigella 
lipopolysaccharides and on the role of macro- 
phage surfaces in the regulation of immune 
response. 

Sierra Leone 

The NIAID and FIC completed an interagency 
agreement with CDC for studies in rural Sierra 
Leone on Mastomys natalensis (a multimammate 
mouse) and Lassa fever. The project character- 
ized the populations of M. natalensis in and 
around villages, determined the relationship of 
genetic subpopulations of mice to transmission 
of Lassa fever to humans, described the epi- 
demiologic and socioeconomic factors associated 
with transmission in the village, and developed 
strategies to prevent rodent-human transmission. 



South Africa 



During FY 1982 the NIAID supported the GML 
through the Gorgas Memorial Institute (Wash- 
ington, D.C.) for investigations in Panama on the 
transmission and reservoirs of the St. Louis virus 
in tropical ecosystems. The GML also collabo- 
rates with the NIAlD-supported Yale Arbovirus 
Research Unit on the epidemiology of the yellow 
fever virus. Intramurally, the NIAID maintains a 
collaborative relationship with the GML on long- 
itudinal studies of viral gastroenteritis in infants 
and young children. 

Papua New Guinea 

The NIAID supports entomologists through a 
domestic grant to the Bernice P. Bishop Museum 
(Hawaii) to collect and characterize larval trom- 
biculidae (Acarina) in Papua New Guinea. NIAID 
scientists are developing a proposal to carry out 
population-based field studies on malaria in 
association with the Papua New Guinea Institute 
of Medical Research. 

Peru 

The Ministry of Health has recognized the 
Instituto de Medicina Tropical ("Alexander von 



The NIAID currently supports a research con- 
tract with the State University of New York 
(Syracuse), which provides for collaboration with 
the Bureau of Biologies (BOB) of the Food and 
Drug Administration, the South African Institute 
for Medical Research (Johannesburg), and the 
University of Cape Town to test the efficacy of 
the new BOB meningococcus, type B polysac- 
charide vaccine in infants and young children 
during the ongoing epidemic of that disease in 
South Africa. Safety and efficacy studies had 
previously been carried out in U.S. children at 
NIAID Vaccine Evaluation Centers at Baylor 
University and the University of Vermont. The 
NIAID continues a long-standing collaboration 
with the Division of Veterinary Services (Onder- 
stepoort) on the systematics and vectors of 
parasitic arthropods. 

Spain 

An NIAID scientist was a member of the four- 
person U.S. team that assisted the Spanish Gov- 
ernment in October 1981 with the investigation, 
management, and control of the toxic poisoning 
associated with an adulterated batch of com- 
mercial olive oil. 



81 



The NIAID Associate Director for Interna- 
tional Research visited the Ministry of Health 
and the Centro Nacional de Microbiologia, Vir- 
ologia, e Immunologia Sanitorias (Majadahonda) 
to discuss opportunities for participation in the 
U.S.-Spain Science and Technology Program. 

Sri Lanka 

An NIAID scientist visited Sri Lanka in Octo- 
ber 1981 in conjunction with a workshop entitled 
"Diagnosis, Evaluation, and Control of Lym- 
phatic Filariasis." 



Sudan 

Through an ICIDR Program project award, 
Michigan State University is collaborating with 
the Ministry of Health on the clinical trials of 
new antischistosomal drugs (e.g. oltipraz), the in 
vitro cultivation and drug-sensitivity testing of 
malarial strains from the Sudan, the ecology of 
Simulium damnosum , and the epidemiology of 
human onchocerciasis. Collaborative arrange- 
ments have been made with the WHO Malaria 
Training Center (Sennar), USAID, Rhone Poulenc 
(Paris), and West German investigators. 

An NIAID scientist visited the Sudan to deter- 
mine whether a collaborative study on leish- 
maniasis might be feasible and to attend a 1-day 
review in Khartoum of the ICIDR project. Col- 
laborative investigators gave presentations re- 
garding administration of the program and 
technical reports on schistosomiasis, onchocer- 
ciasis, and malaria. 

A recent article in Science reported that sera 
collected from individuals living in malarious 
regions of the Sudan not only contained mero- 
zoite-blocking antibodies but also caused intra- 
cellular parasite deterioration and classical 
crisis forms in cultures of P. falciparum . This 
ICIDR award has also produced 6 additional pa- 
pers in press and 12 abstracts of papers present- 
ed or about to be presented at national meetings. 



Sweden 

The NIAID continued discussions with Swedish 
health authorities on bilateral epidemiologic 
research opportunities in the Stockholm County 
Health Care Information System and in the 
NIAID/USAID Regional Project entitled "Epi- 
demiology and Control of Vector-Borne Diseases 
in the Near East." At present, the NIAID and 
Swedish intramural scientists are collaborating 
in two areas: one with the Universities of Lund 
and Uppsala on the molecular aspects of myco- 
plasma-eukaryocyte interactions and the other 
with the University of Uppsala on the structural 
and functional relationships of bacterial antigens 
in the immune response. 



Switzerland 

NIAID intramural scientists are actively col- 
laboratng with Swiss investigators at Basle on 
the immunology and chemotherapy of systemic 
mycoses and at Neuchatel on the natural history 
and public health significance of a previously 
unrecognized rickettsia in the Ixodes ricinus tick 
similar to the Rocky Mountain spotted fever 
agent. An investigator-initiated grant to the 
University of Zurich supports studies on the in 
vitro and in vivo specificity of virus immune T 
cells. A new training grant provides research 
training at the University of Geneva on the 
cloning of murine histocompatibility-2 genes. 

Tanzania 

The Director of the National Institute of Med- 
ical Research (Dar el Salaam) visited the NIAID 
in July 1982. 

Thailand 

The University of Illinois ICIDR Program 
project award involves collaboration with the 
Universities of Cincinnati, New Mexico, and 
Chiang Mai and the McKean Rehabilitation 
Institute. It includes four interrelated areas: 
epidemiology and seroepidemiology of leprosy 
infection and disease, genetic studies of sus- 
ceptibility to leprosy, immunoregulatory abnor- 
malities and immunopathology of leprosy, and 
phagocytic cell functions and metabolism in 
leprosy. 



Trinidad and Tobago 

Rockefeller University has received an NIAID 
grant to continue collaborative studies with 
Trinidadian investigators on the streptococcal 
nephritogenic protein derived from the serum of 
patients with acute, post-streptococcal glomer- 
ulonephritis (AGN). Serum collected from 
healthy children patients with impetigo, and 
AGN will be tested by ELISA and RIA to deter- 
mine the prevalence of this protein at different 
ages, the presence of antibody, and the protec- 
tive role of the antibody against AGN. 

Investigators at Northwestern University and 
the Streptococcal Disease Unit (San Fernando, 
Trinidad) reported in the New England Journal of 
Medicine on a 12-17-year followup on patients 
with AGN in which only 3 of 760 patients dev- 
eloped chronic renal disease. 

U.S.S,R. 

NIAID's formal involvement in the U.S.- 
U.S.S.R. Agreement for Cooperation in the 
Fields of Medical Science and Public Health has 
been limited to influenza. This initiative, under 



82 



CDC coordination, provides for exchange of in- 
formation, scientific meetings, visits by scien- 
tists, and a mutual exchange of virus strains and 
laboratory reagents. During FY 1982 the NIAID 
initiated collaborative activities to identify new 
hepatitis agents with the Institute for Polio- 
myelitis. 

United Kingdom 

The Medical Research Council Clinical Re- 
search Center (Harrow) collaborates with the 
NIAID on the electron microscopy of bacteria 
and on mycoplasma. The London School of 
Tropical Medicine and Hygiene is collaborating 
with the NIAID on the role of bacterial antigens 
in immune response. The NIAID has initiated 
collaboration with the Wellcome Research Lab- 
oratories (Kent) on the developmental adapta- 
tions of T. cruzi in vertebrate immune systems. 
One extramural research grant to the Institute 
of Animal Physiology deals with the genetics of 
response to histocompatibility antigens. Four 
English scientists hold NIAID-supported research 
training grants in diverse areas. 

Venezuela 

Because 9 of the 10 priority areas in the bio- 
medical and epidemiological research component 
of the draft U.S.-Venezuelan Joint Health 
Agreement are communicable diseases, the Di- 
rector, NIAID, has agreed to serve as the interim 
coordinator. In 3uly 1981 visits were made to the 
Pan American Center for Research and Training 
in Tropical Diseases (CEPIALET), the Venezu- 
elan Institute of Scientific Investigation (IVIC), 
the Tropical Medicine Institute (IMT), the Tor- 
realba Institute, the National Institute of Health 
(INH), and "La Trinidad" Medical Teaching Cen- 
ter to determine the present level of scientific 
exchange and opportunities for new and expand- 
ed collaboration. 

The Venezuelan Communicable Disease Coor- 
dinator and Director of CEPIALET has since 
visited the NIAID, and an NIAID scientist at- 
tended a workshop entitled "Immunotherapy and 
Pathogenesis of Leprosy" at CEPIALET. The 
Venezuelan health coordinator and Director, 
INH, visited the NIAID, and the Director of the 
Torrealba Institute initiated discussions on col- 
laborative research in Chagas' disease. 

In August 1982 NIAID scientists spent several 
weeks at CEPIALET to conduct immunologic 
studies on Venezuelan patients with disseminated 
cutaneous leishmaniasis and to evaluate the ef- 
fect of heat therapy in inducing remissions. 
CEPIALET has also initiated joint studies with 
Tulane University on the effect of Albendazole 
in the treatment of patients with onchocerciasis. 
The NIH and CDC have initiated collaborative 
work with the Ministry of Health and Zulia 
health officials to characterize the delta agent 



producing lethal hepatitis among isolated Amer- 
indian populations. NIAID intramural scientists 
continue joint investigations with researchers at 
the University of Caracas in epidemiological, 
clinical, and biochemical studies of human en- 
terviral infection. 

A Venezuelan delegation visited the NIH, the 
FDA, Wistar Institute, and Wyeth Laboratories 
to discuss collaboration on the development and 
production of improved rabies vaccines. 

Zambia 

The NIAID continues long-standing scientific 
exchange with the Tick Diseases Unit (Lusaka) in 
the morphology and classification of African 
specimens. In May 1981 the WHO Team Leader 
of the Tropical Disease Research Center (Zam- 
bia) visited the NIAID. 

Zimbabwe 

Following a visit from the Secretary of the 
Ministry of Health in September 1980, the NIAID 
has begun an exchange of scientific information 
with the Blair Research Institute. An NIAID 
Staff Fellow spent 3 months on the Infectious 
Diseases Service of the University Hospital 
(Salisbury). 



Activities With International Agencies 

NIAID intramural laboratories serve as WHO 
Collaborating Centers in rickettsial diseases, 
mycoplasma, and respiratory viruses other than 
influenza. During FY 1979, WHO designated the 
NIAID Microbiology and Infectious Diseases 
Program as one of three collaborating centers on 
interferon. The NIAID extramural program also 
provides indirect support to U.S. institutions that 
serve as WHO Collaborating Centers. Among the 
most active are WHO Collaborating Centers in 
arboviruses (Yale), enteroviruses (Baylor), in- 
fluenza (CDC and St. Jude's Children's Research 
Hospital), and immunology (Scripps Clinic). At 
the invitation of WHO and TDR, NIAID staff and 
awardees participated actively in meetings or 
expert panels, as consultants to WHO or member 
countries, or as faculty in WHO-sponsored 
training activities. NIAID staff are particularly 
active in support of the WHO Immunology Pro- 
gram, which includes participation in the annual 
WHO Immunology Course in Lausanne. 



Extramural Programs 

The NIAID extramural portfolio in tropical 
medicine is drawn from nine areas of the Micro- 
biology and Infectious Disease Program: the six 
tropical diseases, ICIDR and TRU Programs, 
general parasitology, tropical virology, tropical 



83 



bacteriology, tropical mycology, rickettsiae, and 
vector pathogens. 

Between 1960 and 1980 the NIAID supported 
an ICMR Program, established under the author- 
ity of P. L. 86-610. An ICMR was a research 
organization sponsored by a U.S. health insti- 
tution to provide a stable base for research and 
training through overseas research centers. The 
four ICMR units in Kuala Lumpur (Malaysia), 
Dhaka (Bangladesh), Lahore (Pakistan), and Call 
(Colombia) collectively served as a national re- 
source to provide a pool of tropical disease in- 
vestigators and to stimulate young scientists to 
pursue careers in international biomedical 
research. 

The ICMR Program, however, has been super- 
seded by four award mechanisms that provide 
greater flexibility and cooperation between U.S. 
tropical medicine specialists and their counter- 
parts in developing countries. These mechanisms 
are the International Collaboration in Infectious 
Disease Research Program, the Tropical Disease 
Research Units, the International Tropical Dis- 
ease Research Fellowships, and the Senior In- 
ternational Fellowships with an emphasis in 
tropical diseases. 

The ICIDR Program differs from the ICMR 
Program in several ways. Perhaps the most im- 
portant is the ICIDR emphasis on developing 
peer relationships between U.S. institutions and 
investigators and their counterparts. Its focus is 
on infectious diseases, and at least 7Q percent of 
the award must be spent overseas. The ICIDR 
Program has two parts: the program project 
(Part A) provides grants for collaborative re- 
search in a series of related projects and the 
exploratory project (Part B) divides grants be- 
tween individual scientists in a single area. In 
1982, Part A awards linked Harvard and Cornell 
Universities with the Federal University of 
Bahia, Brazil; the University of Illinois with 
Chaing Mai University in Thailand; Michigan 
State with Central Laboratories of the Sudanese 
Ministry of Health; and the Tulane School of 
Public Health with institutions in Colombia and 
Haiti. Part B developmental grants linked Co- 
lumbia University and the University of South 
Florida with two Brazilian institutions; the Uni- 
versity of Washington with the National Poly- 
technic Institution in Mexico City; Ohio State 
University with the University of Nigeria, Nsuk- 
ka; and the University of Hawaii with the Uni- 
versity of Aligarh in India. 

For many years NIAID intramural laboratories, 
particularly the Laboratory for Parasitic Dis- 
eases and the Rocky Mountain facilities, have 
been committed to basic research in tropical 
diseases. With NIAID support, the Yale Arboviral 
Research Unit also provides a university-based 
center of excellence in tropical virology. The 



NIAID-funded Tropical Disease Research Unit 
Program is designed to expand this network to 
outstanding U.S. institutions through awards for 
multidisciplinary research in tropical medicine. 
In addition to generating new knowledge, the 
TRU Program provides the opportunity for in- 
stitutional strengthening, research training for 
young U.S. and foreign scientists, career devel- 
opment, and a domestic counterbalance to the 
ICIDR initiative overseas. In FY 1982, the TRU 
award to the Peter Bent Bringham Hospital at 
Harvard and to Case-Western University con- 
tinued. 

The ITDR Fellowship Program was initiated in 
1979 with NIAID funds to provide a limited num- 
ber of postdoctoral fellowships for scientists 
from developing countries for advanced U.S.- 
based research training in tropical disease. Ap- 
plications were encouraged from developing 
countries that may not be participating in the 
FIC-supported International Research Fellowship 
Program. The TDR Program has cooperated in 
screening and identifying candidates for ITDR 
fellowships. WHO also provides international 
travel funds for successful candidates it has 
nominated. In FY 1982 an Indian and a Peruvian 
scientist completed the first two ITDR awards 
for research training in leprosy and malaria, 
respectively. Two new awards were made with 
FY 1982 funds for a Chinese and an Egyptian 
scientist to enter schistosomiasis research 
training at the University of Pennsylvania. 

The Senior International Fellowship, with an 
emphasis in tropical diseases, provides 3-12 
months of research support for mid-career and 
senior U.S. scientists to conduct collaborative 
tropical disease research projects outside the 
United States. The initial three awards supported 
research in Kenya, the Netherlands, and the 
United Kingdom during FY 1981-82. 

The Immunology, Allergic and Immunologic 
Diseases Program is the other major NIAID 
extramural awards program. Advances in immu- 
nology have increased lAIDP international ac- 
tivities with most industrialized countries. Rel- 
atively recently, interest has grown in involving 
the larger and/or more advanced developing 
nations such as China, India, Thailand, and Ven- 
ezuela in direct cooperation in immunology or in 
application of new research tools to serious 
endemic disease problems. 

lAIDP now coordinates 18 domestic asthma 
and allergic disease centers and four centers for 
interdisciplinary research on immunologic dis- 
eases. These constitute a network of U.S. in- 
vestigators for research training and collabo- 
ration. lAIDP also supports five lymphocyte 
biology centers and in FY 1982 established the 
first program project at Johns Hopkins Univer- 
sity to study immune function in transplant 



84 



recipients. During FY 1982, the lAIDP Hybrido- 
ma Cell Line Bank, established at the Anrierican 
Type Culture Collection, continued to acquire 
cell lines and began distribution to qualified 
investigators. 

Other lAIDP-supported activities include the 
Allergen Research Reference Laboratory (Mayo 
Clinic), the International Bone Marrow Trans- 
plantation Registry (Mt. Sinai, Milwaukee), and 
the Histocompatibility Seruna Bank. Countries 
participating in these programs during FY 1982 
included China, France, the Federal Republic of 
Germany, 3apan, the Netherlands, Switzerland, 
and the U.S.S.R. 

Non-U.S. scientists may compete for NIAID 
grant awards and apply directly for "sole-source" 
contracts in any program area. Of the 23 awards 
made in FY 1982 to investigators in 10 countries, 
only 3 were relevant to tropical medicine. No 
principal investigator came from a developing 
country. The 23 foreign awards in FY 1982 rep- 
resent a significant decline over the past 3 
years: 27 awards were made in FY 1981 and ^6 in 
FY 1980. 

Although the major functions of the NIAID 
Extramural Activities Program are program 
analysis, project review, and grant or contract 
management, its Research Resources Branch 
also coordinates the Institute's continuing ef- 
forts to provide reagents and resources to in- 
vestigators and government agencies throughout 
the world. During FY 1982 this activity amount- 
ed to 11 major grants or contracts for the dis- 
tribution of microorganisms, parasites, or ani- 
mals for research relevant to tropical medicine; 
in this area, 7 fewer awards were made than in 
FY 1981. Also, reduced costs resulted from 
phase-outs, transfers of functions outside the 
NIAID, consolidations, and the less frequent 
provision of reference materials from intramural 
laboratories. 

In addition to these activities in tropical med- 
icine, this branch continues to provide research 
and reference reagents not available through 
commercial sources for enteroviruses, adeno- 
viruses, rhinoviruses, myxoviruses, the agents 
and antigens of hepatitis A and B, coronaviruses, 
herpesviruses, interferons, mycoplasmas, and 
reoviruses. During FY 1982, arrangements were 
made with the Plum Island Animal Disease Cen- 
ter to process the immune ascitic fluids of Af- 
rican swine fever. Rift Valley fever, African 
horse sickness, and bovine ephemeral fever. 
Complement Compound C3 and penicillin 
products are provided in association with the 
American Type Culture Collection. Hypersen- 
sitivity pneumonitis antigens and antisera are 
being made available in cooperation with the 
Mayo Clinic. Additional allergenic products 
made available include ragweed and rye grass 



antigens and venoms from honey bees, hornets, 
yellow jackets, and other hymenoptera. 

Intramural Programs and Activities 

The NIAID intramural program now has 13 
research laboratories or branches, three of which 
are located at the Rocky Mountain facilities in 
Hamilton, Montana. Although all of these lab- 
oratories have significant international health 
activities, the major portion of tropical medicine 
research is concentrated in the Laboratory of 
Parasitic Diseases. The Epidemiology Branch of 
the Rocky Mountain Laboratory also sets aside a 
substantial portion of its resources for medical 
zoology and vector studies. 

At Bethesda, the Laboratory of Infectious 
Diseases increasingly emphasizes collaborative 
investigations into respiratory viruses, diarrheal 
diseases, and hepatitis. 

Recent advances in immunology and labora- 
tory techniques are now being applied to diseases 
prevalent in the tropics with a consequent 
tendency for broader involvement by basic bio- 
medical research laboratories in international 
research. The Laboratory of Microbial Immunol- 
ogy, for example, is active in studying the im- 
mune reaction to several parasitic infections 
such as trypanosomes, malaria, and amebae in 
experimental models. The Laboratory of Clinical 
Investigation and the facilities at the Clinical 
Center are available for detailed studies on U.S. 
or foreign patients with known or suspected 
tropical diseases. 

While the actual level of intramural research 
in tropical medicine increased by only 7 percent 
between 1981 and 1982, this support is enhanced 
considerably through NIAID intramural inves- 
tigators' collaboration with colleagues outside 
the United States. This joint research extends to 
many areas beyond the scope of tropical medi- 
cine in the exchange of scientists, data, diag- 
nostic material, or the introduction and stand- 
ardization of laboratory techniques. Collabora- 
tion immediately relevant to Tropical Medicine 
also occurs within the NIH and with other Fed- 
eral agencies, particularly the Centers for Dis- 
ease Control, the Office of Naval Research, the 
Walter Reed Army Institute of Research, and the 
Bureau of Biologies. Intramural scientists are 
also involved in the technical work of bilateral 
(USAID), multilateral (WHO, PAHO), or private 
(Rockefeller Foundation, National Academy of 
Sciences) agencies concerned with tropical med- 
icine and internationeil research. 

In FY 1982, 30 intramural projects included 
significant collaboration with scientific insti- 
tutions in 27 foreign countries. The most fre- 
quent collaborators were from France and 



85 



Switzerland, followed by India and the United 
Kingdom. Australia, Canada, Egypt, the Federal 
Republic of Germany, Ghana, and Japan each 
had two cooperating units. One unit also existed 
in Belgium, Brazil, the Dominican Republic, the 
German Democratic Republic, Israel, Italy, 
Panama, Puerto Rico, Sweden, and the U.S.S.R. 



ada, Colombia, Denmark, Hungary, Lebanon, 
Mexico, the Netherlands, the Philippines, Sierra 
Leone, South Africa, the U.S.S.R., and Yugo- 
slavia. 

International Conferences, Seminars, 
and Meetings 



Visiting Program 

The NIAID intramural program benefits con- 
siderably from the participation of foreign vis- 
iting scientists. In FY 1982, for example, the 
NIAID provided funds for 71 long-term visiting 
scientists and 5 experts from 26 countries. The 
NIAID provided laboratory space and reagents 
for 33 guest scientists whose salaries were paid 
by their home institution, government, or source 
other than the NIH. The largest number were 
from Japan (19), the United Kingdom (10), India 
(9), China (8), and Australia (7). Smaller numbers 
represented France (6), Brazil (5), Argentina (4), 
and Taiwan (4). There were three scientists from 
Germany (Federal Republic), Nigeria, and Swe- 
den; two from Israel, Italy, Korea, Switzerland, 
and Venezuela; and one from Bangladesh, Can- 



During FY 1982 the NIAID organized, funded, 
and actively participated in a variety of scien- 
tific meetings relevant to tropical medicine and 
international research. Almost a dozen meetings 
were major national and international meetings, 
conferences, and congresses concerning research 
issues such as interferon, sexually transmitted 
diseases, measles immunization, diarrheal dis- 
eases, and infectious and parasitic diseases. An 
additional l'^ meetings related to bilateral re- 
search programs, 10 of which were associated 
with various activities of boards working under 
the U.S.- Japan Cooperative Health Program or 
programs in Latin America, the Caribbean, and 
the Middle East. Also, a number of conferences, 
seminars, and meetings were held in connection 
with support of research under the auspices of 
such organizations as WHO, PAHO, and USAID. 



86 



Chapter X 
National Institute of Child HeaUh and Human Development 



Introduction 

The mission of the National Institute of Child 
Health and Human Development (NICHD) is to 
conduct and support research on the reproduc- 
tive, developmental, and behavioral processes 
that determine the health of children, adults, 
families, and populations. 

The Institute's programs stem from the as- 
sumption that adult health and well-being are 
determined in part by episodes in early life, that 
human development is a continuous process 
throughout life, and that reproductive processes 
and the management of population problems are 
of major concern, not only to the individual but 
also to the whole of society. 

The NICHD supports research in the repro- 
ductive sciences that enables men and women to 
regulate their fertility with methods that are 
safe, effective, and acceptable to various popu- 
lation groups and to overcome problems of in- 
fertility. In the social and behavioral sciences, 
Institute-sponsored research is aimed at under- 
standing the causes and consequences of popu- 
lation change. Research for mothers, children, 
and families is designed to advance knowledge of 
fetal development, pregnancy, and birth; to 
identify the prerequisites of optimal growth 
through infancy, childhood, and adolescence; and 
to contribute to the prevention and treatment of 
mental retardation. 

The pursuit of new knowledge is basic to the 
Institute's mission. The NICHD regards inter- 
national cooperation as a catalyst for the devel- 
opment of that new knowledge. Through a vari- 
ety of mechanisms, the Institute has maintained 
and expanded its activities in the international 
exchange of scientific information. Activities 
are conducted under bilateral agreements and 
the Special Foreign Currency (P.L. ^^80) Program 
and in cooperation with international agencies 
and the NIH Visiting Program. 

In addition, the NICHD directly supports for- 
eign investigators through research grant and 
contract awards to their home institutions and 
indirectly through awards to U.S. institutions 
with foreign components or involvement in for- 
eign research. 



Summary of International Programs 
and Activities 

Bilateral Agreements and Other 
Country-to-Country Activities 

China 

In January 1979, the United States and China 
signed an Agreement for Cooperation in Science 
and Technology. The agreement, containing 
specific allowances for cooperative activities in 
a number of scientific fields, was furthered in 
June 1979 when health officials from both 
countries signed the Protocol for Cooperation in 
the Science and Technology of Medicine and 
Public Health. Areas of cooperation between the 
NICHD and counterparts in China include human 
genetics, public health and health services re- 
search, child development and nutrition, and 
reproductive physiology and family planning. 

As a followup to the 1981 visit to China by 
NICHD staff participating in the U.S. Delegation 
on Reproductive Physiology and Family Planning 
Techniques, a plan for a study on pregnancy 
outcomes has been designed for implementation 
in Shanghai County. The Institute has forwarded 
the study—which includes perinatal mortality, 
low birth weight, and congenital malforma- 
tions—through channels to the Chinese 
Coordinator. 

India 

In accordance with the Indo-U.S. Bilateral 
Agreement dating from 197^, and in cooperation 
with the U.S. -India Subcommission on Science 
and Technology and the India Council for Medi- 
cal Research, the NICHD staff has participated 
in meetings to advance collaborative research in 
the population sciences and in nutrition. A Work- 
ing Group on Reproduction and Contraceptive 
Research oversees the development of the coop- 
erative program. 



87 



Japan 

The NICHD participates in the efforts of the 
U.S. Malnutrition Panel Program of the U.S.- 
3apan Cooperative Medical Sciences Program by 
supporting research studies intended to develop 
solutions to the nutritional problems of special 
concern to Asian people. 

Nigeria 

In September 1981, Nigeria and the United 
States signed a formal agreement to establish 
cooperative health activities. The plan specifies 
U.S. -Nigeria research collaboration in nutrition, 
beginning with workshops to develop preliminary 
research protocols, followed by workshops in the 
United States that will include Nigerian inves- 
tigators. 

Poland 

Under the U.S.-Poland Collaborative Research 
Agreement, a study of the epidemiology of 
neural tube defects continues at the Krakow 
Institute of Pediatrics. 

Yugoslavia 

A collaborative study of breast cancer as a 
possible result of oral contraceptives is in prog- 
ress with the Institute of Oncology in Ljubljana, 
under the U.S. -Yugoslavia Joint Board for Sci- 
entific and Technological Cooperation. 



Activities With International Agencies 

World Health Organization 

NICHD staff serve as consultants to the WHO 
Special Program of Research, Development and 
Research Training in Human Reproduction and as 
members of the WHO Committee on Resources 
for Research about Human Reproduction. 

Collaborative and cooperative efforts with 
WHO on the development of safe and effective 
methods of fertility regulation for both men and 
women have been extensive. These activities 
range from mutual consultation to joint product 
development. 



European Medical Research Council 

Staff of the NICHD are members of the council's 
Advisory Subgroup on Reproduction, which was 
established to identify areas of cooperation 
within Europe and between Europe and the 
United States on research in reproduction. The 



subgroup also interacts with the pharmaceutical 
industry to obtain information about the indus- 
try's research projects with a possible a bearing 
on human reproduction. 

Extramural Programs 

Components of the NICHD extramural re- 
search program are the Center for Population 
Research, the Center for Research for Mothers 
and Children, and the Epidemiology and Biome- 
try Research Program. 

The Center for Population Research is respon- 
sible for the primary Federal research effort in 
the population sciences. Included are studies on 
human fertility and infertility, the development 
and evaluation of methods of fertility regulation, 
and the social and behavioral aspects of these 
problems in relation to individuals and to popu- 
lations. Through research grants and contracts, 
the NICHD supports investigators around the 
world. 

A research project supported by the Center 
for Population Research is studying the motiva- 
tions and adjustments of migrants from a rural 
region in the Philippines who resettled either in 
Manila, the major urban area of the country, or 
in Honolulu, a key U.S. destination city. The 
study has provided new insights into the reasons 
for moving, the choice of destinations, and the 
effect of migration policies on internal and 
international migration flows. 

Migration decisions, the study shows, are 
based on a complex set of familial and quality- 
of-life consideration, and are not dictated simply 
by economic circumstances. The study found 
that household and family strategies in- fluence 
decisions about moving to a greater extent that 
individual desires do. Out-migrants often 
maintain substantial obligations and con- tinuing 
contacts with their previous households through 
monetary remittances, visits, and cor- 
respondence. The study also confirmed the im- 
portance to decisionmaking of assistance from 
relatives and friends located in different poten- 
tial destinations. 

The Center for Research for Mothers and 
Children supports biomedical and behavioral 
research aimed at making possible pregnancies 
and births that produce sound infants, who can 
grow to adulthood free of disease and disability. 
Since its inception, the NICHD has promoted 
research on the role of nutrition in the preven- 
tion of disease and disability as part of the 
strategy for achieving that goal. 

A nutritional anthropologist is currently 
studying the relationship between culturally 
induced malnutrition in young children and pro- 
tection against malaria in the Sudest Island of 



88 



New Guinea. Malaria, endemic in this area of 
New Guinea, represents a major cause of child- 
hood mortality. Feeding animal protein to 
children under age three is traditionally pro- 
scribed. The resulting malnutrition produced by 
this prohibition may offer protection against the 
malaria Plasmodium, which appears to be more 
sensitive to undernutrition than the human host. 
The current working hypothesis is that tradi- 
tional food taboos among these islanders rep- 
resent a cultural adaptation to the local envi- 
ronment. 

This observation in the field has implications 
for developing more sophisticated single nutrient 
deficiencies in the human host to protect against 
disease. For instance, iron depletion by lacto- 
ferrin in the gastrointestinal tract of human 
newborns may reduce or alter the resident bac- 
terial colonies there. 

The Center for Research for Mothers and 
Children also supports studies on the human 
learning process and communicative disorders. A 
researcher in England is measuring the impact of 
otitis media with effusion (middle ear infection, 
OME) on the educational/communications com- 
petence of English-speaking children. The study 
will determine if persistent OME is associated 
with educational and/or linguistic retardation, 
what types of problems may result, and if ways 
can be found to provide early detection of such 
problems. 

The Epidemiology and Biometry Program is 
collaborating with the Department of Epidemi- 
ology at Ben Gurion University, Beer Sheva, 
Israel, in a study of the effects of westernization 
on infant feeding practices among Bedouin pop- 
ulations undergoing transition from a nomadic to 
a more settled lifestyle. Data are being col- 
lected to test the hypothesis that, as this trans- 
ition takes place, less exclusive breast feeding 
and more bottle feeding and mixed breast and 
bottle feeding will be practiced. This study 
examines the effects of infant feeding, use of 
hecilth services, and other aspects of a changing 
lifestyle on the rate of growth and morbidity 
during the first year of life. 

Collaboration is continuing with the University 
of Trondheim in Norway to study the outcome of 
successive pregnancies. The routine linkage of 
vital record systems in Norway with death rec- 
ord systems, available now for over a decade, 
provides unusual opportunities for epidemiolog- 
ical investigation of birth outcome. Similar 
linkage has occurred more recently in Sweden, 
and the Epidemiology and Research Program has 
developed collaborative contacts with the Uni- 
versity of Uppsala in exploring these data 
systems. 



International Conferences, Seminars, and Meetings 



Collaborative endeavors with WHO in the area 
of fertility regulation continued in 1982 with a 
"Consultation on the Chemical Synthesis of 
Fertility Regulating Agents" held at the NIH and 
cosponsored by WHO and the NICHD. 

NICHD staff attended the European Medical 
Research Council symposium in Paris entitled 
"Epidemiological Aspects of Human Reproduc- 
tion," which included a session on fertility and 
sterility. 

Intramural Programs and Activities 

NICHD intramural scientists engage in in- 
ternational collaboration in research projects 
relevant to their own research interests at the 
NIH. Often these collaborations are formal, 
structured, and endure for many years. For 
example, one NICHD laboratory chief serves as 
genetic coordinator with China under the U.S.- 
China Health Protocol. 

Research opportunities within the Intramural 
Program of the NICHD include clinical studies in 
the areas of human genetics, endocrinology, and 
reproductive physiology, as well as develop- 
mental psychology. 

NIH Visiting Program and Health Scientist 
Exchange Programs 

The NIH Visiting Program provides opportun- 
ities for recent postdoctoral fellows and senior 
scientists from abroad to conduct collaborative 
research in the United States. More than 50 
internationals from a dozen countries were in- 
volved in the NICHD Intramural Research Pro- 
gram during 1982. The usual length of the visit is 
2 to 3 years. In addition to participants in the 
formal Visiting Program, there are a large num- 
ber of foreign visitors who come as guest work- 
ers, whose financial support comes from sources 
other then the NICHD. 

The activities of all these scientists are pur- 
sued in 11 basic science laboratories or clinical 
research branches of the NICHD, including the 
Developmental Pharmacology Branch, the Endo- 
crinology Branch, the Laboratory of Develop- 
mental Neurobiology, the Laboratory of Neuro- 
chemistry and Neuroimmunology, the Laboratory 
of Theoretical Biology, the Human Genetics 
Branch, and the Laboratory of Developmental 
and Molecular Immunity. 



89 



Chapter XI 
National Institute of Dental Research 



5!»i 



Introduction 

In the search for a better understanding of 
oral health and disease—problems that recognize 
no barriers of geography— the promotion of den- 
tal research internationally cannot be separated 
from the promotion of dental research domesti- 
cally. The National Institute of Dental Research 
(NIDR) encourages the programing of grants, 
contracts, and intramural research wherever the 
best data sources and expertise lie. The Institute 
emphasizes staff participation in and support of 
international meetings and the publication of 
proceedings, the funding of foreign grants and 
contracts, and the provision of research oppor- 
tunities for visiting scientists. 

In its mission to support and facilitate re- 
search on the etiology, diagnosis, prevention, and 
treatment of oral diseases and malfunctions, the 
Institute's six major program areas serve as the 
central force for programing: dental caries; 
periodontal diseases; craniofacial anomalies; soft 
tissue, stomatology, and nutrition; restorative 
materials; and pain-control/behavioral studies. 
The Intramural Research Program, organized 
according to basic biomedical disciplinary lines, 
and the National Caries Program invite visiting 
scientists to augment basic scientific investi- 
gations, primarily, and, to a limited extent, 
clinical research projects. 

During FY 1982, the Institute funded nine 
foreign grants in the research areas of dental 
caries, tooth mineralization, pain control, cra- 
niofacial anomalies, and composition of connec- 
tive tissue. In Bethesda, the Institute's intra- 
mural program supported or sponsored 33 Visit- 
ing Fellows, 7 Visiting Associates, and 7 Visiting 
Scientists. They came from 17 countries, 8 in 
Europe, 6 in Asia, 2 in Latin America, and 1 in 
the Near East. 

The Institute encourages a wide exchange of 
scientific information. NIDR Abstracts informs 
dental investigators of current developments in 
special areas of interest. This publication is 
distributed to about 150 foreign colleagues. 
Dental scientists around the world have been 
asked to register their research projects with the 
Dental Research Data Officer of the NIDR for 
inclusion in an annual publication. Dental Re - 
search in the United States and Other Countries. 



Summary of International Programs 
and Activities 

Bilateral Agreements and Other 
Country-to-Country Activities 

Under the auspices of the U.S.-Nigeria Coop- 
erative Health Agreement, the NIDR assisted 
the Nigerian Ministries of Health and Science 
and Technology, as well the WHO, the Federa- 
tion Dentaire Internationale, and the Interna- 
tional Association for Dental Research, in plan- 
ning and conducting the Conference on Dental 
Research Needs and Opportunities in the WHO- 
Region of Africa. The conference was held in 
February 1982 in Lagos, Nigeria, and brought 
together more than 20 countries whose repre- 
sentatives agreed that a WHO International 
Collaborative Center for Dental Research and 
Oral Health would be an appropriate means to 
stimulate and nurture research in this region of 
the world. The Nigerian Government expressed a 
wish to host such a center. The protocol for the 
center is currently being circulated in the region 
to solicit financial support. 



Activities With International Agencies 

The Special Assistant to the Director, NIDR, 
served as a consultant to the USPHS/WHO In- 
ternational Collaborative Study of Dental Man- 
power Systems in Relation to Oral Health Status. 
In that capacity she was a technical advisor to 
the WHO Regional Office for Europe to explore 
the implications of the collaborative study for 
the delivery of dental services in northern and 
western Europe. 

Extramural Programs 

International collaboration during the year 
continued or was initiated between NIDR sci- 
entists and researchers at the following insti- 
tutions by means of grant support: 

• University of New South Wales and the 
Institute of Dental Research, Sydney, Aus- 
tralia (surface structure of oral bacteria); 



90 



• University of Queensland, Brisbane, Aus- 
tralia (surface composition of apatites); 

• McGill University, Montreal, Canada (pro- 
collagens in dental tissues); 

• University of Toronto, Canada (brain stem 
mechanisms and dental pain associated with 
trigeminal nucleus caudalis); 

• College de France, Paris (migration and 
differentiation of neural crest cells); 

• Gothenburg University, Sweden (plaque 
control and healing after periodontal sur- 
gery); and 

• Hebrew University of Jerusalem, Israel 
(mineralization of tooth enamel). 

International Conferences, Seminars, 
and Meetings 

In 1982, 29 NIDR scientists attended and con- 
tributed to 57 meetings in 21 foreign countries 
and 5 continents. Of these meetings, 19 were 
seminars and discussions of collaborative re- 
search. The other occasions were workshops, 
symposia, and conferences such as the Tenth Sao 
Paulo Congress of Odontology and Latin Ameri- 
can Seminar of Odontology-Sao Paulo, Brazil; 
the Twelfth European Leucocyte Culture Con- 
ference-Vienna, Austria; the First Erik Fern- 
strom Symposium (neurology)-Lund, Sweden; a 
Ciba Foundation Symposium (protein chemis- 
try)-London, England; the Third Merieux Con- 
ference on the Pathology of Viral Diseases-Lyon, 
France; the Conference on Genetics of Industrial 
Microorganisms-Kyoto, Japan; and the Interna- 
tional Sociological Association Symposium on 
International Collaborative Research in Health- 
Mexico City, Mexico. The NIDR also provided 
support to enable foreign scientists to give 
papers at four conferences in the United States. 

NIDR staff of the National Caries Program 
planned and hosted the first U.S. meeting of the 
European Organization for Caries Research, in 
Annapolis, Maryland, in June 1982 in honor of 
the tenth anniversary of the establishment of the 
National Caries Program. The Special Assistant 
to the Director chaired the International Rela- 
tions Committee of the International Association 
for Dental Research and participated actively in 
promoting dental research capacity in developing 
countries. She also assisted the Division of 
Health Policy Research and Education at Har- 
vard University through a cooperative assign- 
ment to develop initiatives on international 
aspects of health and human behavior in devel- 
oping countries, and on issues of health science 
policies related to the allocation of resources for 



research in industrialized societies. She prepared 
agenda items on issues of international health 
policy relevant for pursuit by the NIH and/or 
academic institutions. 



Intramural Programs and Activities 

The microbial systematics section of the In- 
stitute continues to collaborate with the Ameri- 
can Type Culture Collection, the Centers for 
Disease Control, the FDA, the VA, and numerous 
researchers in foreign counterpart organizations 
in regard to the worldwide data bank for infor- 
mation on the diverse strains of human oral 
microbiota. 

The system devised for bacteria has now been 
expanded to include other organisms such as 
yeasts, molds, algae, protozoa, and hybridomas 
so that confusing relations among these life 
forms can be systematized and certain contro- 
versial epidemiological data can be clarified. 
Also, to help identify unknown bacteria isolated 
from the mouth, computer-aided patterns or 
matrices have been constructed and are avail- 
able to researchers throughout the world. 

An NIDR scientist is collaborating with an 
Israeli investigator, at the Weizmann Institute, 
who is crystalizing osteonectin—an important 
protein in bone matrix—in order that the pro- 
tein's structure may be analyzed by X-ray dif- 
fraction. Understanding the three-dimensional 
structure of osteonectin will allow scientists to 
determine how the protein accomplishes its 
biological activities. 

Scientists in the NIDR Laboratory of Bio- 
chemistry, collaborating with investigators at 
the University of Monash, Melbourne, Australia, 
are using the long-lasting techniques of organ 
culture devised by the Australians. They are 
studying how cartilage cells synthesize and break 
down, over periods of several weeks, the large 
proteoglycan molecules that act as shock ab- 
sorbers to cushion loads on human joints. 



NIH Visiting Program and Health Scientist 
Exchange Programs 

A Visiting Fellow from Korea is collaborating 
with staff of the Laboratory of Microbiology and 
Immunology, NIDR, in obtaining circular DNA 
from bacteria. Genes in this DNA control the 
ability of bacteria to digest sugars. The genes 
have been cloned into other bacteria so that the 
molecular basis of this genetic process can be 
studied and so that eventually tooth decay can 
be controlled more effectively. 

In the same laboratory, a scientist from the 
New Zealand Dairy Research Institute, Palmer- 



91 



ston North, has shown that a sugar variant 
(2-deoxyglucose) interferes with the ability of 
various bacteria to absorb sugars and makes it 
hard for them to grow. This research is poten- 
tially useful for developing sugar analogues that 
might be added to the diet to reduce tooth decay. 
From herpesvirus type 1, the cause of fever 



blisters, an English expert has isolated a gene 
that codes for a specific protein and has used 
recombinant DNA techniques to introduce this 
gene into a common bacterium so that the bac- 
terium will produce the protein in quantity. 
These preliminary steps may result in the pro- 
duction of a safe vaccine against this disease. 



92 



Chapter XH 
National Institute of Environmental Health Sciences 



Introduction 

During recent decades, sonne of the more 
urgent health problems confronting the general 
population have arisen from human exposure to 
chemical and other physical factors in the en- 
vironment. Health risks emanating from man's 
environment are not a new phenomenon. How- 
ever, with the post-World War II growth in in- 
dustry and commerce and the acceleration of 
industricdization in developing countries, recog- 
nition and concern for the potentially adverse 
effects of environmental agents on human health 
and the ecosystem have become worldwide. 
Public and private organizations throughout the 
world have tried to anticipate and avoid these 
problems through support of environmental 
health research. The National Institute of Envi- 
ronmental Health Sciences (NIEHS) serves as the 
principal U.S. Federal agency for biomedical 
research on the effects of chemical, physical, 
and biological environmental agents on human 
health. The research aims of the NIEHS focus on 
identifying and investigating environmental 
factors that may have deleterious effects on 
human health (e.g., mutations, cancer, lung 
disease, birth defects), on quantifying these 
effects, on understanding the mechanisms of the 
action of toxic agents on biological systems, and 
on developing methods for testing and predicting 
the toxicity of chemicals. Through these efforts, 
NIEHS research provides the basic information 
necessary for establishing disease prevention 
programs. These goals transcend national bound- 
aries, and the NIEHS plays a leading role in the 
organization and development of international 
efforts to meet environmental health problems. 

Summary of International Programs 
and Activities 



Bilateral Agreements and Other 
Country-to-Country Activities 

China 

Cooperation between the United States and 
China in environmental health was initiated 
during 1980 under the U.S.-P.R.C. Agreement 
for Cooperation in the Science and Technology 



of Medicine and Public Health. The NIEHS par- 
ticipates in public health and health services 
research, which includes both environmental and 
occupational health concerns. Exploratory dis- 
cussions with scientists from both countries have 
been held during exchange visits with initial 
discussions centering around cooperation in the 
following areas: biochemical and epidemiological 
research related to asbestosis and silicosis; bio- 
chemical and epidemiological research related to 
heavy metals; development and validation of 
short-term test methods to detect and assess 
carcinogens, mutagens, and teratogens in the 
environment; and the application of standard 
toxicological test methods and the extrapolation 
of laboratory animal data to man. During FY 
1982, an intramural scientist presented a series 
of lectures on biochemical toxicology at the 
Chinese Academy of Medical Sciences in Beijing 
and visited Shanghai to discuss plans for future 
cooperation with scientists from the First Medi- 
cal College of Shanghai, Fudan University, and 
the Shanghai Cancer Institute. 

Egypt 

Cooperation between American and Egyptian 
environmental health scientists is being carried 
out under the auspices of the U.S.-Egypt Joint 
Working Group on Health Cooperation. The 
NIEHS has been assigned responsibility for the 
U.S. Subcommittee on Environmental and Occu- 
pational Health of the 3WGHC. Efforts to date 
have consisted of a workshop held in Egypt in 
early 1980 to identify the biomedical impacts of 
technology transfer. During 1982, a series of 
training workshops involving 2'f U.S. scientists 
and over 100 Egyptian scientists was held In 
Egypt focusing on the following areas: pesti- 
cides, trace metals, radiation, environmental 
management, and mutagenesis. An information 
unit for environmental impact assessment is also 
being established. This project is directed to the 
needs expressed by the Egyptians for information 
on environmental and occupational health. These 
activities are funded largely through the NIH 
Special Foreign Currency (P.L.-'tSO) Program. 

Italy 

Cooperation between American and Italian 
environmental health scientists is being carried 



93 



out under the joint U.S. -Italy Memorandum of 
Understanding signed by the Secretary, DHEW, 
and the Italian Minister of Health in 1977. Since 
that time, there have been several exchange 
visits between scientists of both sides and dis- 
cussions aimed at defining areas of cooperation. 
Under discussion are possible collaborative ac- 
tivities concerned with mutagenicity testing, 
testing of complex mixtures, long-term bioassay 
testing, and quantitative risk assessment. 

In addition to these activities, NIEHS staff 
have been involved in meetings and consultations 
concerned with the explosion of a chemical 
reactor in Seveso, Italy, which resulted in expo- 
sure of a large population to dioxins. 

Japan 

Cooperation between American and Japanese 
scientists on environmental health problems 
takes place under two formal agreements: the 
U.S.-3apan Cooperative Medical Sciences Pro- 
gram and the Agreement on U.S.-3apan Cooper- 
ation in Research and Development in Science 
and Technology. Under the U.S.-3apan Coopera- 
tive Medical Sciences Program, American envi- 
ronmental health scientists participate in the 
Panel on Environmental Mutagenesis and Car- 
cinogenesis chaired by the Associate Director 
for Genetics, NIEHS. 3oint areas of research 
focus on the detection of mutagenic and car- 
cinogenic chemicals using both in vitro and in 
vivo test systems and on monitoring human pop- 
ulations for evidence of exposure to mutagenic 
and carcinogenic chemicals; joint studies on 
carcinogens and mutagens in the diet and dietary 
tract have been particularly productive. To 
further mutual understanding of these issues, a 
U.S.-3apan Workshop on Genetic Toxicology and 
Food Mutagens was held in the United States 
during FY 1982. 

Under the U.S.-3apan Agreement on Coopera- 
tion in Research and Development in Science and 
Technology, the NIEHS participates in the tox- 
icology program area in the counterpart working 
group on health. Exploratory discussions on 
cooperation in this program were initiated in 
1980 and 1981 by an exchange of scientists so 
that they could become familiar with the or- 
ganizations and research programs in this area. 
In the toxicology program area, discussions cen- 
tered on cooperation in the following subjects: 
development and validation of short-term test 
methods to detect carcinogens and mutagens; 
development of methods to test volatile chemi- 
cals; development of methods to study mixtures 
of chemicals; studies on the chemical initiation 
and promotion of cancer; and the development of 
approaches to quantitative risk assessment. 
During FY 1982, the Special Assistant to the 
Director for International Affairs and the 
Assistant to the Deputy Director, Toxicology 
Research and Testing Program, visited 3apan to 



explore further areas of cooperation and for- 
malize the exchange of quantitative data from 
3apanese and U.S. mutagenicity testing pro- 
grams. In accordance with the Memorandum of 
Understanding with the U.S. Department of 
Labor, NIEHS scientists also held extensive 
discussions with the 3apanese Ministry of Labor 
staff regarding scientific procedures relating to 
bioassay protocols and regarding arrangements 
for an exchange of information on chemicals 
tested and test results. 

U.S.S.R. 

Collaboration between Soviet and American 
environmental health scientists is carried out 
under the auspices of two cooperative agree- 
ments between the United States and the 
U.S.S.R. 

Under the U.S.-U.S.S.R. Medical Science and 
Public Health Cooperative Agreement, the 
NIEHS is the lead U.S. agency for environmental 
health. Formal collaboration in environmental 
health research between the United States and 
the U.S.S.R. is in its tenth year. An exchange of 
information and workshops have been held on the 
following topics: developmental toxicology; 
biological effects of metals; behavioral toxicol- 
ogy; and biological effects of physical factors in 
the environment. The proceedings of these work- 
shops were published in both countries, and over 
50 scientific papers have been published by 
American and Soviet scientists on the results of 
environmental health research conducted under 
this agreement. In addition, a Russian-English 
Glossary of Environmental Health Terminology 
was published in both countries to assist com- 
munications between scientists. 

A workshop was held in the United States in 
May 1982, entitled "Nervous System Effects of 
Electromagnetic Waves (0-300 GHz)." Ten U.S. 
scientists and eight Soviet scientists participated 
in the workshop held at the NIEHS. The purpose 
of the workshop was to discuss existing methods 
of evaluating the impact of electromagnetic 
waves in the environment on the central nervous 
system and behavior to select those methods 
that appear to be most sensitive. As a result of 
the workshop, a duplicate project was developed 
to test and standardize the methodological ap- 
proaches to be used for evaluating effects on the 
central nervous system. A scientist from the 
NIEHS and one from the Bureau of Radiological 
Health, FDA, visited the Soviet Union in Sep- 
tember 1982 to discuss specific details and reach 
an agreement on the exact procedures for ex- 
posing the animals and for measuring the above 
parameters. 

The NIEHS also participates in the U.S.- 
U.S.S.R. Agreement on Cooperation in the Field 
of Environmental Protection, which is admini- 
stered for the United States by the Environ- 
mental Protection Agency. The Director, NIEHS, 



9^ 



serves as the DHHS representative to the Envi- 
ronmental Protection Agreement and cochair- 
man of the working group concerned with the 
biological and genetic effects of pollution. 

Activities With International Agencies 

NIEHS staff have been active participants in 
WHO programs for a number of years. In 1975, 
WHO designated the NIEHS as a Collaborating 
Center for Environmental Health Effects. During 
FY 1982, the Institute, under the leadership of 
the Associate Director for Health Hazard 
Assessment, continued to provide advice and 
scientific expertise to WHO headquarters and 
WHO regional offices. 

In 1979, WHO established the International 
Program on Chemical Safety (IPCS), a coopera- 
tive undertaking involving WHO, the United 
Nations Environmental Program, the Interna- 
tional Labor Organization, and their respective 
member states. Since the signing of a coopera- 
tive agreement between the NIEHS and WHO in 
1980, the NIEHS has assumed the function of. 
lead institution within the IPCS for such activ- 
ities as international evaluations of biological 
effects of chemicals and health hazard assess- 
ments, and review and/or validation of methods 
for testing of mutagenicity, carcinogenicity, 
neurobehavioral toxicity, and toxicity to repro- 
ductive function. Assisting NIEHS participation 
in the IPCS is a WHO Interregional Research 
Unit, established at the NIEHS in 1981. 

The objectives of the IPCS are (1) to encour- 
age international cooperation in the evaluations 
of the effects of chemicals on human health and 
on the quality of the environment; (2) to coor- 
dinate chemical testing and toxicological re- 
search to eliminate unnecessary duplication of 
effort; (3) to develop international protocols for 
laboratory testing, epidemiological studies, and 
risk assessment; {^) to develop international 
guidelines and exposure limits for chemicals in 
air, water, and food; and limits for hazardous 
chemicals in workplaces; (5) to develop response 
mechanisms for coping with chemical emergen- 
cies that may be international in scope; and (6) 
to promote training and development of man- 
power in areas and specialties necessary for the 
achievement of program goals. 

The Director, NIEHS, and the Special Assist- 
ant to the Director for International Affairs, 
NIEHS, attended the third Program Advisory 
Committee of the IPCS, held in June 1982 in the 
U.S.S.R. The PAC is responsible for evaluating 
the workplans and progress of the IPCS and for 
providing guidance on the administrative and 
scientific aspects of the IPCS objectives. 

The Associate Director for Genetics chaired 
two working groups held in Geneva during 1982 
to further develop the "IPCS Collaborative Study 
on Short-Term Tests for Genotoxicity and Car- 



cinogenicity." The purposes of the program are, 
on an international scale, to: (1) evaluate in vitro 
short-term tests for mutagenesis and carcino- 
genesis, (2) evaluate short-term in vivo assays 
for mutagenicity, and (3) develop standardized 
protocols for the performance of short-term 
tests for mutagenicity. The choice of chemicals 
and of participating investigators in these stud- 
ies has been finalized, and provisions for dis- 
tributing these compounds have been made. A 
mutagenesis expert from the NIEHS Cellular and 
Genetic Toxicology Branch also participated in 
these meetings. 

In FY 1982, the chief of the Laboratory of 
Reproductive and Developmental Toxicology 
(LRDT) and the Head, Experimental Teratogen- 
esis Section, LRDT, participated in an IPCS/ 
WHO-sponsored workshop, "Methods for the 
Integrated Evaluation of Risks for Progeny As- 
sociated with Prenatal Exposure to Chemicals," 
held in Prague, Czechoslovakia. This workshop 
was part of an ongoing effort to help organize 
and participate in an international effort to 
identify improved laboratory and clinical ap- 
proaches for detecting birth defects. 

Also within the framework of IPCS, the NIEHS 
Office of Health Hazard Assessment (OHHA), in 
collaboration with the WHO Interregional Re- 
search Unit, prepared draft evaluation docu- 
ments on 2,6-toluene diamine and phthalic acid 
esters. These drafts have been transmitted for 
review and revision to a number of national focal 
points for the IPCS. The OHHA is also respon- 
sible for the scientific editing and updating of 
the second volume of a WHO monograph "Prin- 
ciples and Methods for Evaluating the Toxicity 
of Chemicals." 

NIEHS staff also took part in a workshop en- 
titled "Methods for Estimating Exposure, Quan- 
tifying Risk to Human Health, and Predicting 
Chemical Injury to Ecosystems," organized by 
the Scientific Group on Methodologies for the 
Safety Evaluation of Chemicals in July 1982 in 
Rome, Italy. This group is one of the IPCS 
projects operated jointly with the Scientific 
Committee on Problems of the Environment of 
the International Council of Scientific Unions 
and the United Nations Environment Program. 
The objective of the group is to examine meth- 
ods for the predictive evaluation of the adverse 
effects of chemicals on human subjects and 
other forms of life. This was the third such 
workshop. 

In other WHO activities, the Chief of the 
Laboratory of Reproductive and Developmental 
Toxicology, NIEHS, continued as temporary 
adviser to the Toxicology Review Panel of the 
WHO Special Program of Research, Develop- 
ment, and Research Training in Human Repro- 
duction. The review panel meets twice a year to 
consider the potential toxicity associated with 
current and future approaches to contraception. 
The Chief of the Laboratory of Reproductive and 



95 



Developmental Toxicology has also been invited 
by the Office of Occupational Health, WHO, to 
join an international group studying occupational 
hazards to reproductive functions. 

Extramural Programs 



Through its extramural program, the NIEHS 
provided grant support to (1) the State Univer- 
sity of Leiden, Leiden, the Netherlands, to study 
the induction of genetic damage by chemical 
mutagens; (2) the University of Western Ontario, 
London, Canada, to study the nature of lead- 
binding and mercury-binding nuclear proteins; 
and (3) the University of Turku, Turku, Finland, 
to study gastrointestinal and pulmonary meta- 
bolic functions. In addition, the Extramural 
Program provided funds to the WHO Interna- 
tional Program on Chemical Safety in support of 
that cooperative effort. 

International Conferences, Seminars, 
and Meetings 

To provide an opportunity for scientists from 
different countries to exchange research results 
and stimulate scientific collaboration, the NIEHS 
continues to support a number of conferences 
and seminars involving international participa- 
tion. Examples of the types of seminars and 
conferences supported in part by the NIEHS this 
past year include: 

• Joint American-Swedish Workshop on 
Individual Susceptibility to Genotoxic 
Agents in the Human Population 

• Workshop on the Utilization of Mammal- 
ian-Specific Locus Studies in Hazard 
Evaluation and Estimation of Genetic 
Risk 

• Symposium on Psoralens 

• Seminar on the Role of DNA Lesions and 
Promotion in Organ-Specific Tumors 

• Seminar on recent Electrophysiological 
Methods for Evaluation of Neurotoxicity 

Intramural Programs and Activities 

NIEHS scientists from various intramural 
laboratories continue to collaborate with sci- 
entists from a number of different nations. 
Examples of such collaborative efforts, which 
are of mutual benefit and produce information 
important to the Institute's research goals, are 
listed below: 



Comparative Medicine Branch 

The Chief of the Comparative Medicine 
Branch continues as a charter member of the 
International Committee on the Wasting Marmo- 
set Syndrome. This condition bears resemblance 
to protein-calorie deficiency in man, and the 
current focus of attention is on nutrition causa- 
tion. Experimental work in the United States and 
the Federal Republic of Germany has concen- 
trated on diet energy content. Data from 36 
participating institutions in six countries were 
discussed at a recent meeting held in the United 
States. 

Laboratory of Biochemical Genetics 

The head of the Mammalian Mutagenesis Sec- 
tion collaborated with scientists from the Fed- 
eral Republic of Germany to exchange informa- 
tion on chemicals that induce mutations in 
spermatogonia of mice, biochemical screening 
for mutants from offspring of treated mice, and 
screening for cataract mutations in mice. These 
efforts are extremely important to NIEHS in- 
ternational efforts in genetic risk assessment 
and monitoring of human populations. 

Laboratory of Environmental Biophysics 

The laboratory continues to collaborate with 
scientists from the University of Buenos Aires, 
Argentina, on the free-radical metabolism of 
gentian violet by Trypanosoma cruzi. As the 
agent of Chagas' disease, this microbe infects 
millions of people in Argentina and Brazil alone. 
Because Trypanosoma cruzi is carried by a 
species of the assassin bug found in Texas and 
elsewhere in the American South, Chagas' dis- 
ease may become established in this country. 

The chief of this laboratory participated in an 
International Congress on Water and Ions in 
Biological Systems, held in Bucharest, Romania, 
September 1982. The interdisciplinary nature of 
this congress provided a valuable forum for the 
exchange of information with a number of dif- 
ferent countries. 

Laboratory of Environmental Chemistry 

Scientists in the Laboratory of Environmental 
Chemistry are collaborating with scientists from 
the Laboratory of Molecular Biophysics, Oxford 
University, England, concerning the X-ray crys- 
tallographic properties of cocrystalline states of 
dioxin (and related compounds) and selected 
proteins. NIEHS scientists are also continuing 
their collaboration with the Department of 
Pharmacology, University of Urbino, Italy, on 
the development of a radio-immunoassay capa- 
bility for detecting dioxins applicable to the 
Seveso, Italy, dioxin contamination problem; and 



96 



with the Canada Center for Inland Waters on the 
application of this assay to sediments and fish. 
The reliability of this assay as a screening pro- 
cedure is being evaluated and has led to the 
proposal that this become an American Society 
for Testing and Materials standard method. 

Laboratory of Pharmacology 

The Laboratory of Pharmacology continues its 
collaborative research with scientists from the 
University of Dundee, Scotland, in which hor- 
monal effects on perinatal drug metabolism are 
being studied. With scientists from East Ger- 
many and Finland, U.S. scientists are also con- 
tinuing collaborative efforts on drug metabolism 
by isolated skin cells. The laboratory is also 
collaborating with colleagues from China on a 
project exploring the effects of selenium defi- 
ciency on the mitochondrial toxicity of lead. 

Laboratory of Pulmonary Function 
and Toxicology 

Collaborative research efforts are being con- 
ducted with colleagues from China on the muta- 
genic and carcinogenic properties of nickel salts 
and with colleagues from Japan on the role of 
chromosome nondisjunction in the carcinogenic 
activity of diethylstilbestrol and other car- 
cinogens. 

Laboratory of Reproductive and 
Developmental Toxicology 

Collaborative research efforts continued be- 
tween the Laboratory of Reproductive and De- 
velopmental Toxicology and the University of 
Wurzburg, the Federal Republic of Germany, on 
the target organ metabolism and bioactivation of 
the carcinogen, diethylstilbestrol. Collaborative 
efforts with the University of Uppsala, Sweden, 
on experimental studies related to the distri- 
bution and teratology of 2,3,7,8-tetrachloro- 
dibenzadioxin also continued. 

Office of the Director 

The Associate Director of the Office of 
Health Hazard Assessment has remained active 
as a member of the International Joint Commis- 
sion's Committee on the Assessment of Health 
Effects of the Great Lakes Water Quality and is 
involved in the evaluation of water pollutant 
chemicals and their potential health effects on 
the populations in surrounding counties. This 
office also participated in an international study 
on biological tests in the evaluation of mutagen- 
icity and carcinogenicity of air pollutants. The 
objective of this study was to examine the rel- 
evance of short-term and long-term biological 
tests for mutagenicity to the assessment of 



human carcinogenic risk that may arise from 
exposure to air pollution from motor vehicle 
exhausts and coal combustion products. 

The Associate Director for Genetics attended 
several meetings of the Executive Board and 
Commission of the International Commission for 
Protection Against Environmental Mutagens and 
Carcinogens. These meetings were devoted to 
planning ways the commission could develop 
mechanisms to foster scientific interchange and 
programs in test-method development, valida- 
tion, and use in mass-screening programs. 

By interagency agreement, the NIEHS con- 
tinues to support the Environmental Mutagen 
Information Center at the Oak Ridge National 
Laboratory. The center works closely with in- 
vestigators around the world in both obtaining 
and supplying information on environmental 
mutagenesis. The center has over 30,000 bibli- 
ographic entries in its data banks and remains a 
unique worldwide resource for information on 
environmental chemical mutagenesis. 

The NIEHS has also established the Environ- 
mental Teratology Information Center in col- 
laboration with the Department of Energy and 
Oak Ridge National Laboratory. Information on 
teratogenesis is collected, indexed, and made 
available to the biomedical community directly 
from the center or from the National Library of 
Medicine's TOXLINE. The center is a unique 
worldwide resource for information on 
teratology. 



NIH Visiting Program and Health Scientist 
Exchange Programs 

During FY 1982, collaborative research activ- 
ities were carried out in the Institute's intra- 
mural laboratories by 68 Visiting Fellows and 
Scientists. They came from Argentina, Australia, 
Belgium, Canada, China, the German Democra- 
tic Republic, the Federal Republic of Germany, 
Finland, France, Hungary, India, Israel, Japan, 
Korea, Mexico, the Netherlands, New Zealand, 
Poland, Sweden, Switzerland, the United King- 
dom, Yugoslavia, and Taiwan. Examples of col- 
laborative research projects include studies on 
the metabolism of the carcinogen 2-acetylami- 
nofluorene in rabbit pulmonary and hepatic mi- 
crosomes; drug metabolism by isolated lung 
cells; mechanisms of hepatic action of nonster- 
oidal estrogens; the intracellular binding of lead; 
the effects of antioxidants on DNA alkylation; 
the mutagenic and carcinogenic properties of 
nickel salts; mutagenicity test methods; biome- 
try and quantitative risk assessment; neurobe- 
havioral, pulmonary, and reproductive toxicity; 
and the effects of physical factors on the ner- 
vous system. 



97 



These research projects were mutually bene- FY 1982, many administrators and scientists 

ficial and produced scientific information valu- from all parts of the world visited the NIEHS to 

able to the Institute's research goals. Also during be briefed on its programs and activities. 



98 



Chapter Xffl 
National Eye Institute 



Introduction 



About ^0 million of the world's people are 
blind. The great majority of them are in the 
developing nations of Asia, Africa, and Latin 
America, but blindness is unnecessarily prevalent 
in the industrialized regions of the world as well. 
It has been estimated that at least half of all 
blindness can be prevented by well-planned sight 
conservation programs that use resources and 
medical knowledge already available. Mobiliza- 
tion of such resources requires a worldwide 
effort to increase public and governmental 
awareness of the problems of blindness, to pro- 
mote the development of effective programs in 
countries that now lack them, and to increase 
the effective of programs already in existence. 
If a cost-effective method were found to slow 
down the formation of cataracts so that surgery 
could be delayed in the United States by 10 years 
alone, for instance, over $500 million per year 
could be saved. In much of the developing world 
such a new preventive measure could lead to the 
elimination of the backlog of millions who are 
blind because cataract surgery is not logistically 
or economically possible. 

The specific objectives of the National Eye 
Institute (NEI) international program are these: 

• Evaluating available health technologies, 
promoting the most cost-effective inter- 
vention and prevention programs, and 
making these available to affected pop- 
ulations; 

• Conducting collaborative applied research 
studies aimed at developing preventive 
methods for dealing with very specific 
eye disease; and 

• Promoting the controlled clinical evalu- 
ation of research findings that appear to 
be effective. 



Summary of International Programs 
and Activities 

Bilateral Agreements and Other 
Country-to-Country Activities 

India 



Nutritional deficiency is the leading cause of 
blindness in children worldwide. In India alone it 
is said to account for 180,000 cases. Annually 
20,000 children are estimated to become blind 
from nutritional deficiencies, primarily vitamin 
A, with half of these children surviving and the 
other half dying within 1 year. A collaborative 
Clinical Research Center for the Prevention of 
Nutritional Blindness has been established with 
the National Institute of Nutrition in Hyderabad, 
India, to attack this problem. The Center will 
use U.S. and Indian research bases in an applied 
clinical research program. This program will 
identify those children who present the highest 
risk of becoming blind from hypovitaminosis A 
and other concurrent factors, determine prac- 
tical ways to prevent this blinding condition, and 
develop more cost-effective programs that tar- 
get vitamin A prophylaxis to the highest risk 
populations. The following collaborative projects 
will be carried out at the center: 

• Study of the relationship of vitamin A 
status in the development of related 
keratomalacia and blindness in children; 

• Analysis of the role of anterior segment 
collagenase activity in the development 
of keratomalacia; 

• Comparison of the absorption of vitamin 
A in diarrhea treated with and without 
oral rehydration solution; 



99 



• Examination of the relation of vitamin A 
status to immunocompetence and infec- 
tious morbidity; 

• Evaluation of methods for identifying 
subclinical vitamin A deficiency in chil- 
dren; and 

• Determination of risk factors in the 
development of xerophthalmia in children. 

Final approval of the research agreement 
formalizing this collaborative arrangement has 
been received from both the Government of 
India and the United States, and Center activi- 
ties are underway. The NEI has purchased major 
laboratory equipment for the Center under a 
grant from the U.S. Agency for International 
Development. Two Indian scientists have com- 
pleted a visit to the United States for training in 
special laboratory techniques supportive of the 
collaborative projects. Late in the year an NEI 
collaborator visited Hyderabad to participate in 
the initial activities of the first project. Follow- 
up visits by several other NEI collaborators are 
anticipated shortly. 

NEI scientists and consultants continued their 
collaboration with the Indian Government on the 
Indian prevention of blindness programs. The NEI 
continues to provide consultants in operations 
research, biostatistics, and clinical ophthal- 
mology. 

NEI intramural scientists, Indian scientists and 
clinicians from the Aravind Eye Hospital in 
Madurai, and engineers from the National Aero- 
nautics and Space Administration have been 
working for several years to fashion a new in- 
strument for removing cataracts more effec- 
tively. The scientists and engineers have now 
developed and evaluated a technique for removal 
of hard cataracts through a small incision with 
an air turbine device. The instrument has suc- 
cessfully undergone preliminary tests in animals 
as well as in vitro with hard cataracts from 
Indian patients. In 1982 clinical tests were made 
on 30 patients with retinal problems and a poor 
prognosis for vision. After the instrument func- 
tioned without incident during these tests, it was 
turned over to clinicians at the Aravind Eye 
Hospital for further clinical development. 

3apan 

The U.S.- Japan Memorandum of Under- 
standing on Vision Research, signed in April 
1976, provides for an exchange of scientists 
program sponsored by the NEI and the Japan 
Society for the Promotion of Science. Two sci- 
entists per year from each country may be 
selected for the exchange— one short-term (2 
weeks to 3 months) and one long-term (3 months 
to 1 year). Two Japanese scientists traveled to 
the United States under the auspices of this 



U.S.-Japan Memorandum of Understanding 
during FY 1982. 

An assistant professor of anatomy from the 
University of Keio, Tokyo, Japan, is spending 1 
year, beginning in September 1982, working with 
a professor at the Yale University School of 
Medicine. They are collaborating on analyses of 
synaptogenesis of the retina in fetal monkey 
eyes. 

Another professor spent 2 months in the 
United States, beginning in September 1982, 
visiting the NEI's Louisiana State University, and 
the University of California at Berkeley to work 
on techniques for the correction of certain cor- 
neal abnormalities. As a result of this collabo- 
ration, the scientists developed a surgical pro- 
cedure composed of a photokeratometry system, 
epikeratophakia, and thermokeratoplasty to 
correct refractive error. 

U.S.S.R. 

Under the Vision Research section of the 
U.S.-U.S.S.R. Program for Health Cooperation, 
both sides continued work in the following 
problem areas: 

• Use of Q-switched laser in the treatment 
of glaucoma; 

• Assessment of critical flicker fusion to 
determine optic nerve function; 

• Assessment of gratings to determine optic 
nerve function; and 

• Clinical studies of ENKAD treatment of 
retinitis pigmentosa. 



Activities Witli International Agencies 

In FY 1982, the NEI continued its activities as 
a WHO Collaborating Center for the Prevention 
of Blindness, and the Director, NEI, continued to 
serve as a member of WHO's Special Advisory 
Panel on the Program for the Prevention of 
Blindness. This group has been established to 
advise WHO in its efforts to eliminate blindness 
from the world's population. At the annual 
meeting in Geneva, Switzerland, the advisory 
group discussed several major topics: 

• Program activities, both regional and 
global; 

• Activities of the WHO Collaborating 
Centers for the Prevention of Blindness; 

• Low-cost eyeglasses project; 

• Strategic approaches to prevent blindness; 



100 



• Information systems; 

• Collaboration with nongovernmental 
organizations: current status and future 
approaches; and 

• Membership of the WHO Program Advi- 
sory Group on the Prevention of Blindness. 

Over the past year, the Program for the Pre- 
vention of Blindness, which is supported pri- 
marily by the NEI, has expanded its collection of 
data on blindness and its causes. During FY 1982, 
for example, several additional surveys of 
blindness were developed for Asia and Latin 
America. 



Extramural Programs 

In FY 1983, the NEI made 22 awards to foreign 
institutions in eight countries. The research and 
training projects supported were representative 
of outstanding research projects in all of the 
Institute's major research programs: retinal and 
choroidal diseases; corneal diseases; cataract; 
glaucoma; and strabismus, amblyopia, and visual 
processing. Both basic and clinical research 
projects were included. Some examples follow: 

• To compare various forms of cataract, 
scientists at the Oxford (England) Eye 
Hospital have been conducting a clinical 
trial involving more than 300 patients. 
The results of this study, which will be 
available in about 3 years, are expected 
to define optimal surgical procedures for 
cataract extraction and patient optical 
rehabilitation. The potential applicability 
of these findings is significant because 
cataract is a leading cause of blindness 
and cataract intervention programs are 
conducted worldwide, particularly in 
undeveloped countries. 

• Glaucoma is another leading cause of 
blindness around the world. The reduction 
of blindness resulting from the disease, 
which depends upon development and 
effective distribution of antiglaucoma 
drugs, requires a better understanding of 
the neuropharmacology of the eye. Two 
world-renowned scientists at the Univer- 
sity of Uppsala, Sweden, have contributed 
significantly to developing basic know- 
ledge of the physiology and pharmacology 
of the eye. Their findings have led to 
development and testing of new drugs for 
this devastating eye disease. 

• Tens of thousands of infants are born each 
year with congenital cataracts. Although 
the number and scope of programs for 



cataract extraction have been increasing 
worldwide, only a small number of chil- 
dren with congenital cataracts are 
treated early in life. The result is an 
irreversible visual deficit for many chil- 
dren. To define the critical period in 
visual development beyond which irre- 
versible vision loss occurs, investigators 
at the Hospital for Sick Children in 
Toronto, Canada, are evaluating children 
who have had congenital cataracts ex- 
tracted. Results from these studies will 
help define the optimal time for inter- 
vention. Such information will help eye 
surgeons and health care delivery organ- 
izations set priorities among the various 
social and economic factors that affect 
blindness intervention programs in devel- 
oping countries. 



International Conferences, Seminars, and Meetings 



The Director of the NEI participated in a 
course entitled "Community Eye Health" at the 
Department of Preventive Ophthalmology, In- 
stitute of Ophthalmology, University of London. 
At this course he presented a seminar on clinical 
trials. 

A joint WHO/NEI informal workshop on cata- 
ract epidemiology was held at the NEI in June 
1982. Most of the participants at this workshop 
were representatives of WHO Collaborating 
Centers for the Prevention of Blindness. Because 
of the rapidly growing impact of cataract, due to 
the generally increased life expectancy and 
aging of populations in developing countries, the 
possible prevention of this disease is gaining 
more attention. In this context, epidemiological 
studies are of particular importance. To assess 
possible risk factors in the formation of cata- 
ract, the participants discussed the following 
topics: 

• Available epidemiological data; 

• Identification of risk factors; 

• Classification of cataract; 

• Biochemical aspects of cataract epide- 
miology; and 

• Designs for cataract research. 

The NEI helped support the WHO Annual 
Course on Immunology and Infectious Disease at 
Lausanne, Switzerland. This course presents a 
unique opportunity to assemble the finest immu- 
nologists from the developing world. Before 
NEI's participation, ocular immunology had not 
been included in the course. In 1982, the course 
offered the opportunity for scientists to discuss 
various aspects of ocular autoregulation, ocular 
immunoregulation, and ocular parasitic disease. 
It is hoped that the course will interest re- 



101 



searchers because onchocerciasis, leprosy, and 
toxoplasmosis are major problems in these de- 
veloping countries. 

The NEI is cooperating with the U.S. Commit- 
tee of the International Agency for the Preven- 
tion of Blindness in planning its Second General 
Assembly. Over 61 countries and 250 individual 
participants will gather in Bethesda, Maryland, 
October 2k through 28, 1982, for this global 
conference, which will be the largest gathering 
of experts on blindness prevention ever con- 
vened. The theme of the assembly, "New Hori- 
zons in Sight," reflects the fact that the lAPB's 
original goal—the creation of national commit- 
tees throughout the world for the prevention of 
blindness—is almost fully achieved and that 
many of these committees have been successful 
in initiating sight conservation programs in their 
countries. At this assembly the results achieved 
by many of these programs will be evaluated, 
and the most successful ones identified as mod- 
els for other countries to follow in the develop- 



ment of their programs. It is hoped that by dem- 
onstrating the substantial progress achieved to 
date, this assembly may convince governments 
of developing countries that well-designed 
blindness prevention programs should be sup- 
ported where they are needed. If this message is 
successfully conveyed, the chances are greater 
that the battle against preventable blindness 
worldwide can be won. 



NIH Visiting Program and Health Scientist 
Exchange Programs 



The NEI continued to serve as an international 
center for research and research training in eye 
diseases. Thirty-six Visiting Scientists, Fellows, 
and other researchers from 17 different coun- 
tries around the world participated in research 
projects at the NEI campus in Bethesda in FY 
1982. 



102 



Chapter XIV 
National Institute of General Medical Sciences 



Introduction 

The National Institute of General Medical 
Sciences (NIGMS) gives financial support for 
research and research training to a number of 
basic biomedical science disciplines that under- 
gird the disease-specific initiatives of the cate- 
gorical NIH Institutes. 



Extramural Programs 

The NIGMS accepts designated grant appli- 
cations, which fall within its mission to support 
basic biomedical research, from principal in- 
vestigators at appropriate institutions in coun- 
tries other than the United States; and it funds 
those with the highest scientific merit. Eight 
such grants were funded during FY 1982 to 
principal investigators in four countries: Argen- 



tina, Canada, Israel, and the United Kingdom. 

The foreign grants were funded by four In- 
stitute programs, namely, the Cellular and Mo- 
lecular Basis of Diseases Program, the Genetics 
Program, the Pharmacological Sciences Pro- 
gram, and the Physiology and Biomedical Engi- 
neering Program. 



International Conferences, Seminars, and Meetings 



The NIGMS joined other Institutes at the NIH 
to provide foreign travel funds for American and 
foreign scientists to participate in two inter- 
national conferences: the Twelfth International 
Congress of Biochemistry, held in August 1 982 at 
Perth, Australia; and the International Confer- 
ence on Streptococcal Genetics, held in Novem- 
ber 1981 at Sarasota, Florida. 



103 



Chapter XV 
National Institute of Neurological 
and Communicative Disorders and Stroke 



The National Institute of Neurological and 
Communicative Disorders and Stroke (NINCDS) 
serves as the unit of the NIH responsible for 
basic and clinical research on disorders of the 
nervous system and of human communication. 
Through its research grant program, application 
of P.L. ^80, which permits use of U.S.-owned 
foreign currencies in specific countries and 
collaborative research projects engaging the 
NINCDS scientists and their foreign colleagues, 
the Institute maintains a continuing interaction 
with international neuroscientists. Because 
neurological and communicative disorders are 
major problems in virtually every country of the 
world, all nations stand to benefit from inter- 
national research efforts and interchange of 
knowledge. Further, some of the neurological 
disorders vary in incidence and severity from 
country to country. The study of these variations 
and identification of their causes should lead to 
a clearer understanding of the causes of the 
disorders themselves. Therefore, the potential 
impact of international neuroscience research is 
great. 

Summary of International Programs 
and Activities 

Bilateral Agreements and Other 
Country-to-Country Activities 

In FY 1982, the NINCDS had a number of 
informal agreements in effect. In addition, the 
Institute began negotiations with the Govern- 
ment of Italy for epidemiological studies of 
stroke and the dementias. 

In 1982, the NINCDS sponsored four P.L.-^80 
projects. Two of these projects were in Poland, 
and two were in Egypt. Both Polish projects 
concerned neuromuscular disorders, one being a 
study of the role of neurological cells in the 
processes of myelination and demyelination, and 
the other a study of the degree of muscle lesion 
in different disease conditions, as well as the 
connection between endocrine and muscle dis- 
turbances. The Polish groups, located at the 



Medical Academy of Warsaw and at the Medical 
Academy in Poznan, have access to virtually all 
cases of neuromuscular disease in Poland and are 
a valuable international research resource. 

The two remaining P.L.-^80 projects were 
both in Egypt. One concerned perinatal screening 
of developmental malformations; the other was a 
study of the venoms of poisonous snakes. The 
perinatal screening project, in which over 
100,000 patients in Cairo and Mansura have now 
been studied, has revealed a higher than ex- 
pected incidence of spina bifida and anenceph- 
aly. Data from this project are undergoing a 
comprehensive analysis to discover the reasons 
for the higher incidence. The snake venom study, 
involving collection of venoms from North and 
East Africa as well as from Egypt, has resulted 
in publication of six scientific papers in journals 
outside Egypt and has put the Government of 
Egypt in a position to manufacture good anti- 
venins for North and Central Africa. 



Activities With International Agencies 



Since 1975, the NINCDS has been one of 13 
WHO Collaborating Centers in the Neurosci- 
ences. These centers, positioned strategically 
throughout the world, further international re- 
search efforts on neurological disorders and 
initiate and demonstrate community programs 
for prevention and treatment of these disorders. 
Special emphasis is being given to the cerebro- 
vascular disorders (stroke), the convulsive dis- 
orders (epilepsy), and the neurological and com- 
municative disorders related to nutritional and 
developmental problems of children. The other 
12 Collaborating Centers in the Neurosciences 
are: 

• The Laboratoires d'Etudes et de Recher- 
ches Synthelabo, Paris, France 

• The Arthur Vining Davis Center for Be- 
havioral Neurobiology, The Salk Institute, 
San Diego, California 

• The Montreal Neurological Institute, 
Montreal, Canada 



10^ 



• The Groupe Hospitaller de la Timone, 
Marseilles, France 

• The Fundacion Institute Neurologico de 
Colombia, Bogota, Colombia 

• The Clinique Neurologique, Dakar, Senegal 

• The University of Ibadan, Ibadan, Nigeria 

• The Institute of Neurology, The Academy 
of Medical Sciences of the U.S.S.R., Mos- 
cow, U.S.S.R. 

• The Centre Medical Universitaire, Ge- 
neva, Switzerland 

• The Institute Nacional de Neurologia y 
Neurocirugia, Mexico City, Mexico 

• The Shanghai First Medical College, 
Shanghai, China 

• The Beijing Neurosurgical Institute, 
Beijing, China 

Each center funds its own activities and in- 
cludes collaborative research, publications for 
scientific information exchange, support of 
conferences and courses, advisory services, 
technical assistance, and training of new inves- 
tigators. 

As part of this effort, the NINCDS, the NIH 
Fogarty International Center, and WHO jointly 
sponsor an International Neurosciences Fellow- 
ship Program. This program provides men and 
women from developing countries with stipends 
for advanced training in the United States so 
that they can assume leadership roles in aca- 
demic and public health careers in the neuro- 
sciences in their own countries. In 1982, the 
NINCDS supported five international neurosci- 
ence fellows from China, four at the NIH and 
one at the University of Minnesota Medical 
School. 

The NIH Visiting Program 

During FY 1982, the NINCDS intramural pro- 
gram was host to 85 Visiting Scientists, Visiting 
Associates, and Visiting Fellows from 58 coun- 
tries. Represented were Argentina, Australia, 
Austria, Bangladesh, Belgium, Bolivia, Brazil, 
Canada, Chile, China, Colombia, Czechoslovak- 
ia, Denmark, Egypt, Finland, France, the Federal 
Republic of Germany, Ghana, Greece, Guate- 
mala, Guyana, Hong Kong, Hungary, India, Iran, 
Ireland, Israel, Italy, Jamaica, 3apan, Korea, 
Luxembourg, Mexico, Nepal, the Netherlands, 
New Zealand, Nigeria, Norway, Pakistan, Pan- 
ama, Peru, the Philippines, Poland, Portugal, 



Sierra Leone, South Africa, Spain, Sri Lanka, 
Sweden, Switzerland, Turkey, the U.S.S.R., the 
United Kingdom, Uruguay, Venezuela, Yugo- 
slavia, Zimbabwe, and Taiwan. 

The contributions of these investigators add 
immeasurably to the strength and effectiveness 
of the NINCDS Intramural Program, and the 
experience and new knowledge they take back 
with them to their home countries strengthen 
the neurosciences around the world. 

Extramural Programs 

NINCDS awarded 21 foreign research grants in 
FY 1982 to institutions in Canada, Israel, Italy, 
Mexico, New Zealand, Sweden, and the United 
Kingdom. These grants supported both clinical 
and basic research and have been awarded to 
outstanding investigators exploring problems of 
high priority in the United States and in their 
own countries. 

the University of Western Ontario received 
the largest NINCDS foreign grant in 1982 for the 
gathering and analysis of data from approxi- 
mately 60 U.S. and foreign medical centers on 
the effectiveness of a surgical procedure for 
preventing strokes. The procedure—known as the 
extracranial/intracranial bypass—involves graft- 
ing a scalp artery to an intracranial artery to 
improve blood supply. Although the technique is 
widely practiced, it is not statistically proven to 
be better than other forms of treatment. By 
1983 the results of this study will be available to 
neurosurgeons and stroke specialists in cill 
countries. 



International Conferences, Seminars, and Meetings 

In 1981, the Institute provided some support 
for the World Federation of Neurology Meetings 
in Tokyo, 3apan. Several staff members attend- 
ed. In 1982, the First International Brain Re- 
search Organization World Congress on the Brain 
in Health and Disease was held in Lausanne, 
Switzerland. The NINCDS provided support for 
planning this meeting. In addition, the XII Sym- 
posium Neuroradiologicum— held in Washington, 
D.C., in 1982— was partially supported by an 
NINCDS grant and attracted visitors from many 
countries. 



Intramural Programs and Activities 

Work continues on development of new anti- 
convulsant drugs, combining the efforts of 
pharmaceutical firms in Europe and Japan. Two 
promising drugs, one from Japan and one from 
France, are now being tested under NINCDS 
contracts. The NINCDS Epilepsy Branch con- 



105 



tinues to work with Epilepsy International to 
innprove the use of anti-epileptic drugs. A team 
from the NINCDS Epilepsy Branch is working 
with the WHO Neurosciences Collaborating 
Center in Mexico to evaluate a protocol for 
studying the pharmacokinetics of anticonvulsant 
drugs in non-Caucasian populations, particularly 
in developing countries. 

The NINCDS Laboratory of Central Nervous 
System Studies continues research on the slow, 
latent, virus-induced brain disorders such as 



Creutzfeldt- Jakob disease and on Korean 
hemorrhagic disease with renal syndrome. In 
reference to the latter, scientists have demon- 
strated the presence of the causative agent in 
North American rodents. 

A continual interchange occurs among 
NINCDS intramural and foreign scientists on 
topics of interest, not only through scientific 
meetings but also through visits to laboratories 
and consultations with scientists doing related 
work. 



106 



Chapter XVI 
Warren G. Magnuson Clinical Center 



Introduction 



The Warren G. Magnuson Clinical Center (CC) 
was authorized by Congress to provide the high- 
quality patient care necessary to conduct bio- 
medical research. The 5^6-bed hospital has fa- 
cilities and support services for nearly 1,000 
physicians who conduct clinical research for 8 of 
the 11 NIH Institutes and for the National In- 
stitute of Mental Health. Since its establishment 
nearly 30 years ago, the CC has served as a 
prototype for many research hospitals. It was 
specially designed to place patient care facilities 
close to research laboratories to promote quick 
transfer of new findings of basic and clinical 
scientists to the treatment of patients. More 
than 'f,000 patients are admitted annually (upon 
referral by their personal physicians); and in 
accordance with increasing emphasis on pre- 
vention and ambulatory health care, outpatients 
are now observed and treated at a newly opened 
ambulatory care research facility. 

The CC ensures the highest possible level of 
medical care to each patient; provides optimal 
resources and facilities for clinical research; 
performs research on methods and systems in- 
volved in patient care and study; disseminates 
information to professionals and to the public 
relevant to clinical investigation; develops and 
maintains training programs in the techniques 
and ethics of biomedical and clinical research; 
and interacts with scientists and physicians, 
nationally and internationally, on such mutual 
problems of clinical research as policy, educa- 
tion, ethics, and priorities. 

Summary of International Programs 
and Activities 

Bilateral Agreements and Other 
Country-to-Country Activities 

A French-American-British (FAB) Coop- 
erative Group is developing a uniform classi- 
fication of acute leukemias and myeloprolifer- 
ative syndromes that will be useful in the prog- 
nosis and treatment of patients with these dis- 
eases. The group is composed of seven bone 



marrow morphologists: two from the United 
Kingdom, three from France, and two from the 
United States. The Chief of the CC Hemotology 
Service is one of the U.S. representatives. 

NIH Visiting Program and Health Scientist 
Exchange Programs 

A Japanese expert consultant has begun a 
2-year project to purify the NANB virus (des- 
cribed above) and to develop a NANB test sys- 
tem. This area is crucial to further clinical 
studies of this agent. 

Development of assays to detect different 
agents for hepatitis and additional epidemiologic 
information should decrease the risk of hepatitis 
following blood transfusion and permit selection 
of low-risk blood donors for safer blood products. 

The Clinical Center Blood Bank has been in- 
volved in several international collaborative 
research projects in the hepatitis area in FY 
1982. The primary goals have been evaluation of 
data concerning posttransfusion hepatitis in 
different populations, collaborative efforts to 
identify markers for posttruansfusion hepatitis, 
and exchange of scientific informaton and ex- 
perience about posttransfusion hepatitis, a dis- 
ease that has a significant worldwide distribution. 

The risk oif transmitting hepetitis through 
blood is affected by a variety of factors—social, 
economic, and ethinic. A cooperative sutdy was 
undertaken to compare the fequency of hepatitis 
viral antigens and anitbodies among blood donors 
in the U.S.S.R. and the United States. The re- 
sults permit calculation of age and sex preval- 
ence of hepatitis B and hepatitis A serologic 
markers for blood donors within and between 
each country, as well as comparison, on the same 
sera, of test methodologies in use in both 
countries. 

No accepted assay is available for the agent 
that transmits non-A, non-B (NANB) hepatitis. A 
coded panel of NANB infectious sera and ap- 
propriate controls was distributed to investi- 
gators in the United Kingdom, France, the Fed- 
eral Republic of Germany, and Costa Rica. Blood 
Bank investigators have been responsible for the 
collation and interpretation of results that have 
identified a candidate assay. 



107 



Chapter XVH 
Division of Computer Research and Technology 



Introduction 

Established in 196'^, the Division of Computer 
Research and Technology (DCRT) was designed 
to make computational methods a tool for the 
NIH biomedical community. Over the years, the 
work of the Division has become an integral part 
of the conduct and management of NIH research 
programs. At the same time, the DCRT has 
grown to become the largest biomedical com- 
puting facility in the world. DCRT staff mem- 
bers continue to create still more powerful and 
useful systems. They continually seek new ways 
to bring computers, mathematics, and engi- 
neering into the service of science and to en- 
hance administrative effectiveness. 

Summary of International Programs 
and Activities 



Activities With International Agencies 

In a study sponsored by WHO, the Data Man- 
agement Branch collaborated with a researcher 
from Nigeria in creating a data base for exam- 
ining the prevalence of major neurological dis- 
eases in that country. 



Extramural Programs 



DCRT staff members collaborated with sci- 
entists from foreign countries including Aus- 
tralia, Canada, China, France, Ghana, Green- 
land, 3apan, Nigeria, and Singapore. Examples of 
these international collaborative activities 
include: 

• Computer support for flow microfluoro- 
metry /cell sorters (Europe and Australia) 

• Statistical research in clinical pathology 
(Belgium and Japan) 

• Multivariate statistical analysis (Australia) 



• Theory and measurement of intermolec- 
ular forces (Canada) 

• Analysis of coupled transport and bio- 
chemical kinetics (France) 

• Prevalance of major neurological diseases 
(Nigeria) 

Other visitors to the DCRT throughout the 
year included foreign scientists from China, the 
Federal Republic of Germany, and the Republic 
of South Africa. 



International Conferences, Seminars, and Meetings 



The Division cosponsored, with the European 
Society of Cardiology and others, the annual 
conference on Computers in Cardiology. At this 
forum physicians, engineers, and computer sci- 
entists exchange information on the design of 
computer systems and their application to 
cardiology. 

A delegation of foreign scientists attending 
the Sixth Annual Conference on Computers in 
Chemistry and Education came to visit DCRT 
for a briefing on the varied work of the Division. 
Countries represented by this group included 
Austria, Belgium, Canada, China, the Federal 
Republic of Germany, Finland, France., Hungary, 
Israel, Japan, Sudan, Switzerland, the United 
Kingdom, and the U.S.S.R. 



Intramural Programs and Activities 

The Data Management Branch is designing a 
system for the computerization of data on bio- 
medical scientists and institutions in China. 
Officials at the FIC will use the system to brief 
NIH and non-NIH scientists interested in bio- 
medical research in that country. 

The Branch also designed a system that allows 
the FIC to maintain and query a data base that 
contains information on foreign scientists who 
are in the United States to perform health 
research. 



108 



An FIC Fellow in the Laboratory of Applied applied successfully to patients under intensive 
Studies of the DCRT has contributed to the care following myocardial infarction, 
theory of dynamic risk assessment in acute dis- 
ease by creating very general, yet practical, nuj Visiting Program and Health Scientist 
methods for sequential analysis of time-depend- 
ent multivariant measurement vectors obtained Exchange Programs 
during the course of a patient's illness. Combin- 
ing these methods with discriminant function Three foreign scientists, two from Israel and 
techniques enables daily reassessment of prob- one from Belgium, continued to work at the 
able patient outcome. The procedures have been Division during FY 1982. 



109 



Chapter XVm 
Division of Research Resources 



Introduction 

The Division of Research Resources (DRR) 
develops and supports a variety of multicate- 
gorical, interdisciplinary research resources 
essential to biomedical research. These re- 
sources are used by a broad spectrum of inves- 
tigators to enhance their own effectiveness and 
that of their institutions in responding to and 
carrying out the mission of the National Insti- 
tutes of Health. The DRR comprises five major 
programs: (1) General Clinical Research Centers, 
(2) Biotechnology Resources, (3) Minority Bio- 
medical Research Support, (4) Biomedical Re- 
search Support, and (5) Animal Resources. 

Of these, the Animal Resources Program 
(ARP) is the most involved in international ac- 
tivity. The ARP provides researchers with ani- 
mals that are essential for studies on human 
disease processes and physiological systems. The 
ARP is also concerned with the study and pres- 
ervation of animal populations in their natural 
environments. The ARP consists of two subpro- 
grams: the Primate Research Centers Program 
(PRCP) and the Laboratory Animal Sciences 
Program (LASP). The PRCP supports seven re- 
gional primate research centers and the LASP 
supports specialized animal models and colonies, 
as well as a variety of other animal resource 
projects. Several of these projects are conducted 
outside the United States. 

Summary of International Programs 
and Activities 



Bilateral Agreements and Other 
Country-to-Country Activities 

Of increasing international concern is the 
preservation of declining nonhuman resources to 
support biomedical research at a time of ex- 
panding agricultural and industrial development. 
To address this issue, the IXth Congress of the 
International Primatological Society was held 
August 8-13, 1982, in Atlanta, Georgia. It was 
hosted by the Yerkes Regional Primate Research 
Center and attended by over 700 scientists and 
other individuals interested in primatology re- 
search, including about 30 representatives from 



10 countries that are original habitats for vari- 
ous species of nonhuman primates. Overall, the 
congress was considered highly successful and a 
number of publications related to primate con- 
servation will result. 



Extramural Programs 

The Yerkes Primate Center, a grantee of the 
PRCP, provides support to the Kenyan Primate 
Center, Kenya, East Africa, for establishment of 
a base of information on African primate species 
(particularly the baboon in its native habitat); 
for exchange of information on these animals; 
and for research projects related to the survival 
of these animals in their native habitat. 

The PRCP provides support through the Wash- 
ington Regional Primate Research Center for 
Indonesian primate research activities at the 
Kutai Field Station. The orangutan, gibbon, and 
other primates native to this part of the world 
are endangered or threatened species whose 
habitats are rapidly being destroyed by industrial 
and agricultural development in Indonesia. This 
support is important for the development of 
information related to the survival of these 
species and the continued availability of these 
important species for use in biomedical research. 

The LASP supports a project in northern India 
that focuses on population studies of nonhuman 
primates. This project, initiated in 1959 and 
supported by ARP since 1973,has provided data 
regarding population dynamics and demographic 
and reproductive parameters of a natural rhesus 
monkey population. One study group has in- 
creased 16.8 percent in numbers in the 't years 
since the export ban on rhesus monkeys, com- 
pared with an increase of 16.5 percent in the ^ 
years prior to the ban. Since populations with 
good birth rates and low infant mortality rates 
can increase at the rate of 16 percent per year, 
the rhesus population could have been expected 
to increase at least 50 percent since the ban. 
The actual figures indicate that similar factors 
influenced the population both before and after 
the ban and that export per se has not been a 
dominant factor. Ongoing studies will provide 
data on the effects of habitat displacement, 
which is occurring with one study group, and the 
feasibility of intentional transplants and relo- 



110 



cation of breeding groups. Such information is 
necessary as a guide to conservation and man- 
agement of rhesus monkeys and will be impor- 
tant in evaluating the potential supply of rhesus 
monkeys for biomedical research. 

A second project supported by the LASP in- 
volves the study of important habitat features of 
West African rain forest primates. This project 
includes a detailed examination of the relation- 
ships between feeding behavior, specific eco- 
logical conditions, and social organization. It is 



essentially a predictive study in which important 
variables such as foraging styles, diet selection, 
home range, group size patterns, population 
density, distribution, and social interaction are 
expected to relate in specific ways to ecological 
conditions. The information will be useful, not 
only to behaviorists, socio-ecologists, and bot- 
anists, but also to conservationists and those 
making decisions about the size of forest areas 
in Africa necessary to maintain wild populations 
of primates. 



HI 



Chapter XIX 
Division of Research Services 



Introduction 

Through collaboration and cooperation with 
national and international organizations, the 
Division of Research Services (DRS) plans and 
conducts centralized programs of scientific, 
engineering, and technical services in support of 
biomedical research activities. Professional and 
technical staff members consult with research 
scientists during all stages of a research project 
on the development and use of essential products 
and services. DRS personnel provide specialized 
assistance and services in biomedical engineering 
and instrumentation design and development; 
research animal production, maintenance, pro- 
curement, and animal disease identification and 
control; provide biomedical library and trans- 
lation services; and make available specialists in 
medical arts and photography. 

The DRS is involved internationally in such 
activities as developing a primate supply pro- 
gram for biomedical research; establishing 
training programs in conservation and manage- 
ment of wild primates; supplying organizations 
and institutions throughout the world with ge- 
netically defined rodents as nuclei for colony 
development; sponsoring the development of 
methods for primate population studies and 
surveys; developing programs to train techni- 
cians in scientific instruments and to establish 
repair and maintenance centers in six univer- 
sities in Egypt; and developing a regional pro- 
gram for repair and maintenance of hospital 
clinical care equipment in the eastern Caribbean 
countries of Barbados, St. Lucia, St. Vincent, 
Montserrat, St. Kitts, Antigua, and Dominica. 

The DRS has detailed to the Department of 
State a senior staff member, who has been as- 
signed to the U.S. Embassy in New Delhi, India, 
as the U.S. Scientific Attache and International 
Health Representative. In this assignment he 
assists the Scientific Counselor in all matters 
relating to U.S. scientific affairs in India with 
specific responsibility for representing, moni- 
toring, and coordinating the program interests of 
the U.S. Department of Health and Human Ser- 
vices and other U.S. agencies engaged in health 
and health-related activities. 



Summary of International Programs 
and Activities 

Bilateral Agreements and Other 
Country-to-Country Activities 

Agreement with 3apan on Cooperation in 
Research and Development in Science 
and Technology 

In April 1980, a collaborative project in lab- 
oratory animal science was instituted as part of 
the U.S. -Japan Non-Energy Cooperative Agree- 
ment. The purpose of the project is to promote 
the exchange of information on laboratory ani- 
mal models, the development and use of uniform 
international standards for research animals, and 
the exchange of information on other aspects of 
laboratory animal science. The DRS has respon- 
sibility for U.S. involvement in this project. 

Initially, the purpose of the project was to 
develop information on quality control of lab- 
oratory animals. Several workshops on quality 
control provided material to be used in a series 
of U.S./3apan laboratory animal quality control 
manuals. In addition, representatives from both 
countries have actively participated in work- 
shops on genetic and microbiological monitoring. 

Egyptian Ministry of Health 

On April 17, 1980, an agreement was signed 
between the Egyptian Ministry of Health and 
DHHS. Under a Special Foreign Currency Proj- 
ect, the Egyptian Ministry of Health, in coopera- 
tion with the Biomedical Engineering and In- 
strumentation Branch, National Institutes of 
Health, DHHS, will develop a pilot repair and 
maintenance center for medical equipment. This 
center will service a cross-section of Ministry of 
Health medical facilities in Giza. It is antici- 
pated that the center, after suitable modifica- 
tions, will serve as a model for a program in the 
repair and maintenance of medical equipment 
applicable nationwide in Egypt. 

During 1980, the American Project Officer 
and the Egyptian Principal Investigator met to 



112 



develop an operating plan for the center and an 
implementation plan for the project. Project 
implementation began in 1981 with the training 
of center personnel— both in Egypt and the 
NIH--the purchase of equipment supplies for the 
center, and the construction of a building to 
house the center on the grounds of Hamwandia 
Hospital. The center became operational in 1982. 

By the end of FY 1982, the center had devel- 
oped repair capacity in excess of that required 
to service Hamwandia Hospital alone; therefore, 
consideration is being given to increasing the 
number of hospitals and clinics serviced by the 
center. 

Under an interagency agreement with the 
National Science Foundation, the Biomedical 
Engineering and Instrumentation Branch, DRS, 
assisted five Egyptian universities in the devel- 
opment of repair and maintenance centers for 
scientific equipment. This project was carried 
out under an agreement between the USAID and 
the Egyptian Academy of Scientific Research 
and Technology providing for assistance "to help 
organize and direct the Egyptian scientific com- 
munity toward dealing with the practical prob- 
lems inhibiting economic development and social 
improvement." 

Caribbean 

Under a Participating Agency Service Agree- 
ment with USAID, the Biomedical Engineering 
and Instrumentation Branch is (1) participating in 
a joint effort with Project Hope to improve the 
repair and maintenance capability of the Jamai- 
can Ministry of Health biomedical equipment 
repair facilities and develop a biomedical equip- 
ment maintenance program at the College of 
Arts, Science and Technology in Kingston and (2) 
developing a cooperative regional program for 
the maintenance hospital clinical care equipment 
for the islands of the eastern Caribbean. The 
program in the eastern Caribbean will be tai- 
lored to meet the individual needs of the coun- 
tries involved and will make full use of existing 
repair capability, both in the private and in the 
public sectors. The implementation plan calls for 
the development of two repair centers within the 
region to provide repair services throughout the 
region. To date, this branch has made site visits 
to the countries involved to determine their 
repair and maintenance needs, purchased an 
inventory of basic maintenance tools and equip- 
ment for each of the islands, reviewed the cap- 
ability of existing repair and maintenence per- 
sonnel in the region, and selected personnel for 
training in instrument maintenence. 



Activities with International Agencies 

World Health Organization: Resource of 
Laboratory Rodents 

The NIH genetic resource of laboratory ro- 
dents has been designated as a collaborating 
center for defined laboratory animals by WHO, 
and as an international nude mouse reference 
center by the International Council on Labora- 
tory Animal Science. The resource maintains 
over 200 stocks and strains of genetically de- 
fined and monitored rodents and rabbits and 
serves as a source of breeding nuclei of animals 
used by NIH research investigators as well as by 
the international biomedical research communi- 
ty. Approximately 6,000 animals were supplied 
to domestic and foreign research institutions in 
FY 1982. 

World Health Organization: Primate Supply 
Program 

A contract has been established with WHO to 
develop an international primate supply program. 
WHO is to provide expert consultation and ad- 
visory assistance to the governments of coun- 
tries interested in taking measures to ensure the 
continuing availability of nonhuman primates for 
use in biomedical research. This contract is 
intended to implement recommendations made 
by the Interagency Primate Steering Committee 
as outlined in the National Primate Plan. 

The NIH has a critical interest in the contin- 
uing supply of nonhuman primates. Intramural 
research programs at the NIH use more non- 
human primates than any other government 
organization. In addition, NIH extramural re- 
search requires one-third of the total animals 
used for health-related programs. Another major 
user group is the pharmaceutical/biological 
industry, where nonhuman primates are required 
for the production and testing of drugs and bio- 
logic products that are licensed and controlled 
by the FDA. Because primate populations are 
rapidly declining, and because these animals are 
important to human, health-related needs, the 
objectives served by the WHO contract are of 
the utmost importance. 

Pan American Health Organization 

The Interagency Primate Steering Committee, 
through a contract with PAHO has developed 
projects to establish New World primate breed- 
ing centers and conservation programs in Latin 



113 



American countries. Although the majority of 
these countries imposed restrictions on the com- 
mercial export of nonhuman primates in 1973, 
they are interested in providing those species 
required for biomedical research through captive 
breeding and controlled wildlife management 
programs. 

Specific objectives of the contract are: 

• To provide expert consultants and advice 
to Latin American governments inter- 
ested in developing primate programs as 
recommended by WHO; 

• To assist in developing national programs 
of wild primate conservation and man- 
agement to ensure the perpetuation of 
natural nonhuman primate resources; and 

• To support development of primate 
breeding stations to produce species im- 
portant to biomedial research under cap- 
tive or semicaptive conditions. 

The fully established Peruvian National Pri- 
mate Project includes a breeding station in 
Iquitos, as well as field management activities. 
Marmosets and squirrel monkeys have been pro- 
vided from this operation for use in U.S. biomed- 
ical activities since 1976. 

An agreement was also established between 
PAHO and the Government of Colombia to de- 
velop a captive owl monkey breeding station at 



Armero and to assist in ongoing conservation 
programs. Primate breeding and conservation 
programs have also been initiated in Brazil. 
These programs will eventually become self- 
supporting through funds received for primates 
made available for scientific use. 

In addition to contract support, DRS staff 
provided consultive services in FY 1982 to sev- 
eral South American countries on matters re- 
lated to primate conservation, breeding, and 
nutrition. These services are part of the overall 
cooperative effort to ensure the availability of 
nonhuman primate species as animal models for 
human disease. 

NIH Visiting Program and Health Scientist 
Exchange Programs 

A Visiting Scientist from England was re- 
cruited to establish an NIH program in zeugma- 
tography, a technique for medical diagnostic 
imagery based on the principles of nuclear mag- 
netic resonance (NMR). Since his arrival in No- 
vember 1977, he has conceived and designed an 
entirely new method for producing three- 
dimensional NMR images. Moreover, he has 
successfully tested several major components of 
the system, and its first images are expected 
within the next few months. In addition, since his 
arrival, he has made numerous significant con- 
tributions to the scientific literature of NMR 
imaging. 



llt^ 



Appendix 
Definitions of NIH International Program Activities 



Research Awards 



Foreign Research Grants 

The NIH supports research projects outside the 
United States only when they have met special 
criteria established for foreign grants. These 
criteria include the highest scientific merit and 
relevance to the program interests of the NIH as 
well as conformance with NIH, DHHS, and other 
U.S. policies. 



Cooperative Agreement Awards 

Cooperative agreement awards are 
noncompeting research grants to support 
collaborative projects between sponsoring 
Institutes and principal investigators, usually 
conducted under a formal protocol. 



Core Grant to Gorgas Memorial Institute 

A core grant to the Gorgas Memorial 
Institute/Gorgas Memorial Laboratory in Panama 
is appropriated through the budget of the FlC, 
NIH. The GML conducts research in tropical 
diseases of importance to Central America and 
the United States. 



Domestic Grants With Foreign Components 

A domestic grant with a foreign component is 
an NIH-financed grant with a domestic 
investigator in which a part of the grant is used 
to support research in a foreign country. 



International Collaboration in Infectious Diseases 
Research Awards 

Under the International Collaboration in 
Infectious Diseases Research Program, emphasis 
is given to developing relationships between U.S. 
institutions and counterpart institutions abroad 
in infectious diseases research. The ICIDR 
Program was begun in 1979 when the Inter- 



national Centers for Medical Research, which 
had existed from 1962, were phased out. In table 
A-1, the data for ICJDR awards are reported 
with other "Domestic Grants With Foreign Com- 
ponents." In tables A-2 and A-3, ICIDR awards 
are reported separately. 



International Scientific Meetings 

The NIH assists in the support of scientific 
meetings held to coordinate, exchange, and 
disseminate information when such activities are 
directed toward objectives clearly within the 
areas of NIH program interests. Activities 
reported include international components of 
those meetings supported under this research 
program area. 



Special Foreign Currency (P.L. 480) Grants 

The Special Foreign Currency Program, 
administered by the FIC, enables the NIH to 
support overseas activities that contribute to the 
advancement of health sciences in the United 
States. Funded by U.S. -owned local excess 
currency primarily derived from the sale of 
surplus U.S. agricultural commodities, these 
activities include biomedical research and the 
translation and dissemination of scientific 
literature. Funds for the Special Foreign 
Currency Program are appropriated to the 
Office of the Assistant Secretary for Health, 
DHHS, and awarded and administered by the NIH. 



Foreign Contracts 

Research contracts with institutions outside 
the United States must comply with the criteria 
prescribed for foreign grants. 



Domestic Contracts With Foreign Components 

A domestic contract with a foreign component 
is an NIH-financed contract with a domestic 
institution in which a part of the contract is used 
to support research in a foreign country. 



115 



Scientist Exchanges 



Visiting Fellows, Associates, Scientists 

The NIH Visiting Program offers talented 
scientists throughout the world the opportunity 
to share the research resources of the NIH. 
Through this program, distinguished scientists at 
all levels of their careers are invited to the NIH 
to receive further research experience and to 
conduct research in their biomedical specialties. 



International Research Fellowships 

The FIC International Research Fellowship 
Program provides awards to foreign scientists in 
the formative stages of their careers to come to 
the United States for up to 2 years of advanced 
research training. Fellows are required to return 
to their respective home countries at the 
termination of their fellowships. 



Scholars-in-Residence 

The FIC Scholars-in-Residence Program has 
been developed to facilitate the work of indi- 
vidual scholars and the exchange of ideas among 
scholars, distinguished science leaders, and sci- 
ence administrators. Scholars-in-Residence are 
nominated by NIH scientists and spend up to 10 
months in residence at the NIH. 



States, or persons who have been lawfully 
admitted to the United States for permanent 
residence. With acceptable justification, these 
fellowships may be taken at foreign institutions. 
Fellowships are not awarded for study leading to 
the M.D., D.D.S., D.V.M., or other applied 
science degree. 



Foreign Work/Study Assignments 

The Foreign Work/Study Program involves 
overseas work assignments developed by NIH 
professionals not only to meet their own training 
and experience needs, but also to contribute to 
the domestic and/or international goals of the 
DHHS. Potential assignments are developed 
directly with foreign institutions, U.S. 
organizations having overseas installations, or 
other appropriate organizations that can provide 
a foreign work/study experience to fulfill 
program objectives. 



International Travel 

International travel is defined as travel by NIH 
personnel, traveling under DHHS travel orders, 
to locations outside the United States, including 
Canada and Mexico, to attend international 
meetings and to participate in multilateral 
organization (e.g., WHO, PAHO) activities. This 
category also includes travel under bilateral 
exchanges. 



Senior International Fellowships 

The FIC Senior International Fellowship 
Program provides opportunities for established 
U.S. faculty members, who have demonstrated 
productive scholarship and achieved recognized 
stature in their profession, to go abroad to 
conduct collaborative research and to share their 
expertise. It is intended that this award be a 
career-enhancing educational experience with 
mutual benefits to both home and host 
institutions. 



National Research Service Awards 

Under NIH National Research Service Awards, 
predoctoral, postdoctoral, and special 
fellowships to promote training for research in 
health-related sciences are granted each year to 
U.S. citizens, noncitizen nationals of the United 



BID Program Support 



Bilateral Exchanges 

Bilateral exchanges not only contribute to 
advancement of biomedical and behavioral 
science for the benefit of health in the United 
States, but also serve the purposes of (1) 
overcoming social or political barriers (e.g., 
China, U.S.S.R.), (2) fostering sharing of 
technical resources and expertise (e.g., France, 
Israel, Japan), (3) drawing on unique resources or 
settings (e.g., India, Nigeria), and (k) furthering 
U.S. foreign policy objectives (e.g., Egypt, 
Kuwait). NIH participation is geared to scientific 
benefits to be derived. Funding, which is 
dependent on competition with other program 
needs, is derived from regular BID operating 
funds. 



116 



Figure A-1.— NIH international activities, funding by mechanism, FY 1982 

(in millions of dollars) 




International 
Travel 
($1.6) 



Special Foreign 

Currency (P.L. 480) 

Grants ($1.4) 



FY 1982 Total for International Activities: $62.1* 



*lncludes $3.7 of ''Other Funds" — i.e., not appropriated to NIH 



117 



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121 



Table A-2.--NIH international research and research training awards 
by country /area and mechanism,^ FY 1982 

(in thousands of dollars) 



Total 



Research 
grants 



Cooperative 
agreements 



ICIDR 



SFCP 
(P.L. *80) 



Research 
contracts 



Country /area number amount number amount number amount number amount number amount number amount 



Argentina 

Australia 

Austria 

Bangladesh 

Belgium 

Bolivia 

Brazil 

Canada 

Chile 

China 

Colombia 

Denmark 

Egypt 

Finland 

France 

Germany, F.R. 

Ghana 

Greece 

Guatemala 

Guyana 

Hong Kong 

Hungary 

India 

Iran 

Ireland 

Israel 

Italy 

Jamaica 

Japan 

Korea 

Lebanon 

Luxembourg 

Mexico 

Nepal 

Netherlands 

New Zealand 

Nigeria 

Norway 

Pakistan 

Panama 

Peru 

Philippines 

Poland 

Portugal 

Romania 

Sierra Leone 

South Africa 

Spain 

Sri Lanka 

Sudan 

Sweden 



21* 
1*5 

5 

3 
18 

1 

13 

122 

S 
38 

2 
12 

7 
21* 
t*2 
21 

2 
10 

1 

3 

11 

121 

2 

6 

103 

9^ 

2 

20^ 

12 

2 

3 

13 
1 
22 
9 
8 
5 
1 

3 
3 
22 
2 
1 
2 

23 
2 
2 

52 



1*52 

1,731 

79 

1*0 

357 

1*0 

1,2^3 

7,W9 

151 

750 

t*65 

21*7 

1,01*1 

532 

698 

637 

26 

170 

18 

75 

132 

3,070 

30 

13^ 

^^,^19 

1,575 

15 

3,^93 

173 

30 

1*7 

213 

21* 

t*3i* 

182 

W* 

31* 

6 

57 
71 

t*3\ 
20 
25 
21 

133 

1*51* 
18 

382 
1,773 



21 



60 



38 
3 

3 
1 



118 
1,301 



133 



^,311 11 



\0i* 



250 

73 

130 



2,130 
82 

28 
12 



68 

1^5 
58 



25 



35 



^72 



1,053 



1*1*7 



\t* 


1,981 


1 


195 


1 


31*5 


1 


28 


1 


258 


1 


13 



52 12 



1,283 



7 1,262 
1 \i*5 

3 1*32 



36 



73 



t*2 



355 



19 



1,228 



122 



Table A-2.~Continued 





Visiting 


Int'l Research 


Guest 


Senior Int'l 




Nat'l Research 




ProRtam 
number amount 


Fellows 


Researchers 
number 


Fellows 




Service 
number 


Awards 


Country/area 


number amount 


number amount 


amount 


Argentina 


14 


194 


6 


140 


(7) 


^ 


. 


. 


. 


Austredia 


13 


250 


9 


153 


(11) 


1 


9 


1 


18 


Austria 


t^ 


53 


1 


26 


(7) 


- 


- 


- 


- 


Bangladesh 


3 


40 


- 


- 


(1) 


- 


- 


- 


- 


Belgium 


10 


129 


5 


95 


(6) 


- 


- 


- 


- 


Bolivia 


1 


40 


- 


- 


- 


- 


- 


- 


- 


Brazil 


3 


45 


7 


145 


(7) 


- 


- 


- 


- 


Canada 


27 


485 


- 


- 


(16) 


1 


26 


9 


134 


Chile 


2 


19 


5 


117 


- 


1 


15 


- 


- 


China 


31 


437 


6 


118 


(22) 


- 


- 


- 


- 


Colombia 


1 


18 


. 


- 


(1) 


- 


_ 


- 


- 


Denmark 


6 


57 


4 


86 


(5) 


- 


- 


- 


_ 


Egypt 


5 


71 


1 


25 


(2) 


- 


- 


- 


- 


Finland 


6 


62 


11 


192 


(2) 


- 


- 


- 


- 


France 


24 


354 


9 


167 


(22) 


1 


13 


5 


91 


Germany, F.R. 


14 


181 


- 


- 


(29) 


1 


16 


3 


52 


Ghana 


1 


13 


- 


- 


- 


- 


- 


- 


- 


Greece 


10 


170 


- 


- 


(3) 


- 


- 


- 


- 


Guatemala 


1 


18 


- 


- 


- 


- 


- 


- 


- 


Guyana 


- 


- 


- 


- 


(2) 


- 


- 


- 


- 


Hong Kong 


3 


75 


- 


- 


(1) 


- 


- 


- 


- 


Hungary 


11 


132 


- 


- 


(2) 


- 


- 


- 


- 


India 


102 


1,623 


6 


112 


(15) 


- 


- 


- 


- 


Iran 


2 


30 


- 


- 


- 


- 


- 


- 


- 


Ireland 


1 


18 


5 


116 


(1) 


. 


- 


- 


- 


Israel 


47 


785 


5 


114 


(13) 


3 


75 


3 


53 


Italy 


80 


1,140 


7 


155 


(49) 


3 


53 


- 


- 


Jamaica 


2 


15 


- 


- 


- 


- 


- 


- 


- 


Japan 


192 


2,827 


5 


132 


(51) 


- 


- 


1 


14 


Korea 


10 


134 


1 


27 


(5) 


- 


- 


- 


- 


Lebanon 


1 


5 


1 


25 


- 


- 


- 


- 


- 


Luxembourg 


3 


47 


- 


- 


(1) 


- 


- 


- 


- 


Mexico 


6 


39 


4 


70 


(2) 


- 


- 


- 


- 


Nepal 


1 


24 


- 


- 


- 


- 


- 


- 


- 


Netherlands 


16 


221 


3 


55 


(6) 


- 


- 


- 


- 


New Zealand 


5 


54 


3 


70 


- 


- 


- 


- 


- 


Nigeria 


4 


47 


4 


64 


(2) 


- 


- 


- 


- 


Norway 


1 


17 


4 


76 


(5) 


- 


- 


- 


- 


Pakistan 


1 


6 


- 


- 


- 


- 


- 


- 


- 


Panama 


- 


- 


- 


- 


(1) 


- 


- 


- 


- 


Peru 


1 


18 


2 


39 


(2) 


- 


- 


- 


- 


Philippines 


3 


71 


- 


- 


(1) 


- 


- 


- 


- 


Poland 


18 


327 


4 


104 


(5) 


> 


- 


- 


- 


Portugal 


2 


20 


- 


- 


(1) 


- 


- 


- 


- 


Romania 


- 


- 


- 


- 


- 


- 


- 


- 


- 


Sierra Leone 


2 


21 


- 


- 


- 


- 


- 


- 


- 


South Africa 


3 


91 


- 


- 


- 


- 


- 


- 


- 


Spain 


13 


243 


9 


176 


(4) 


- 


- 


- 


- 


Sri Lanka 


2 


18 


- 


- 


(1) 


- 


- 


- 


- 


Sudan 


- 


- 


1 


27 




- 


- 


- 


- 


Sweden 


17 


245 


11 


210 


(9) 


2 


30 


3 


60 



123 



Table A-2.— Continued 



Total 



Research 
grants 



Cooperative 
afireements 



ICIDR 



SFCP 
(P.L. ttSO) 



Research 
contracts 



Country /area number amount number amount number amount number amount number amount number amoun 



Switzerland 3i^ 607 

Tanzania 2 51 

Thailand 2 k70 

Turkey 2 k2 

United Kingdom [3tt 3,^97 

United States U6 3,177 

Uruguay 1 24 

U.S.S.R. 

Venezuela 2 51 

Yugoslavia 17 352 

Zimbabwe 1 17 

Taiwan 10 168 

Stateless 

Unspecified 9 118 



International Organizations 



EORTC 
lARC 
lUAC 
PA HO 
WHO 

Total 



428 
2,884 

609 
1,080 

752 



18 



199 

29 

77tt 

46 



1 441 



141 



127 
5 



1,512 48,113 197 11,411 



1 
15 



215 
504 



692 
1,925 



1 50 
8 943 

1 13 



213 
2,380 

482 

1,074 

60 



2,384 19 1,424 53 10,608 



124 



Table A-2.~Continued 





Visiting 


Int'l Research 


Guest 


Senior Int'l 




Nat'l Research 




Program 
number amount 


Fellows 


Researchers 
number 


Fellows 




Service Awards 


Country/area 


number amount 


number amount 


number amount 


Switzerland 


17 


190 


5 


35 


(12) 


k 


97 


4 66 


Tanzania 


1 


1 


- 


- 


- 


- 


- 


- 


Thailand 


- 


- 


- 


- 


- 


- 


- 


- 


Turkey 


2 


k2 


- 


- 


(2) 


- 


- 


- 


United Kingdom 70 


1,070 


5 


69 


(16) 


12 


260 


21 381 


United States 


[i^(> 


3,177 


- 


- 


(9) 


- 


- 


- 


Uruguay 


- 


- 


1 


2k 


(2) 


- 


- 


- 


U.S.S.R. 


- 


- 


- 


- 


(2) 


- 


- 


- 


Venezuela 


1 


38 


- 


- 


(f) 


- 


- 


- 


Yugoslavia 


8 


1^3 


1 


22 


(2) 


- 


- 


- 


Zimbabwe 


1 


17 


- 


- 


- 


- 


- 


- 


Taiwan 


8 


114 


2 


55 


(2) 


- 


- 


- 


Stateless 


- 


- 


- 


- 


(1) 


- 


- 


- 


Unspecified 


- 


- 


- 


- 


- 


- 


- 


9 118 


International ( 


Drganizations 














EORTC 


. 


_ 


. 


_ 


_ 


«. 


. 


_ _ 


lARC 


- 


- 


- 


- 


- 


- 


- 


- 


lUAC 


- 


. 


. 


- 


- 


- 


. 


- 


PAHO 


- 


- 


- 


- 


- 


- 


- 


- 


WHO 


- 


- 


- 


- 


- 


- 


- 


- 


Total 


979 


15,722 


153 


3,061 


(372) 


29 


593 


59 985 



NOTE: Numbers in parentheses are not added into totals. 
Totals may not add due to rounding. 



1 



Table A-2 includes only those categories in table 1 that constitute research and research training awards. 



125 



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127 



Index by Country 



Argentina, 19, 25, ^1, ^2, 44, 58, 59, 86, 96, 97, 

105 
Australia, 2, 7, 14, 19, 20, 25, 41, 58-60, 63-65, 

67, 72, 74, 86, 91, 97, 103, 105, 108 
Austria, 19, 38, 41, 65, 71, 91, 105, 108 
Bangladesh, 62, 65, 74, 84, 86, 105 
Belgium, 19, 25, 41, 59, 65, 71, 86, 97, 105, 

108, 109 
Bolivia, 105 
Brazil, 2, 19, 25, 37, 41, 42, 44, 45, 58, 69, 72, 

74-76, 84, 86, 91, 96, 105, 114 
Canada, 2, 7, 20, 39, 41, 44, 45, 46, 58, 59, 65, 

67, 71, 72, 86, 91, 96, 97, 101, 103-105, 

108, 116 
Chile, 19, 20, 42, 44, 58, 72, 105 
China, 3, 4, 6, 7, 11, 14, 15, 19, 20, 25, 26, 29, 

35, 36, 43, 45-47, 59, 62, 65, 72, 74, 76, 

84-87, 89, 93, 97, 105, 108, 116 
Colombia, 6, 41, 42, 44, 67, 74, 84, 86, 105, 114 
Denmark, 14, 19, 41, 58, 86, 105 
Dominican Republic, 7, 73, 11., 86 
Egypt, 2, 4, 20, 22, 24, 25, 29, 35, 36, 41, 43, 

47, 67, 68, 72, 74, 11, 86, 93, 104, 105, 

112, 113, 116 
Finland, 1, 19, 25, 41, 44, 47, 63, 64, 72, 96, 

97, 105, 108 
France, 7, 14, 18-22, 25, 30, 35-37, 41, 43, 

46-48, 59-61, 63-65, 67, 71, 72, 74, 85, 86, 

91, 97, 104, 105, 107, 108, 116 
Germany, 11, 14, 18, 20, 21, 25, 29, 31, 35, 36, 

41, 43, 45, 46, 48, 59, 64, 65, 67, 72, 1% 

78, 85, 86, 96, 97, 105, 107, 108 
Ghana, 41, 65, 74, 78, 86, 105, 108 
Greece, 25, 41, 59, 65, 72, 105 
Guyana, 105 

Hong Kong, 7, 15, 59, 71, 105 
Hungary, 21, 22, 25, 29, 31, 35, 36, 41, 65, 72, 

86, 97, 105, 108 
Iceland, 41 
India, 2, 6, 14, 19, 22-25, 41, 49, 59, 62, 65, 

67, 68, 72, 74, 78, 79, 84, 86, 87, 97, 99, 

100, 105, 110, 112, 116 
Iran, 41, 105 
Ireland, 19, 59, 105 
Israel, 2, 14, 19, 20, 25, 39, 41, 43, 44, 45, 49, 

50, 58, 59, 63-65, 67, 71, 72, 74, 79, 86, 

89, 91, 97, 103, 105, 108, 109, 116 
Italy, 2, 14, 19, 20, 25, 26, 29, 32, 35, 36, 41, 

43, 46, 50, 59, 64, 65, 67, 72, 79, 86, 

94-96, 104, 105 
Jamaica, 45, 58, 59, 105 
Japan, 2, 3, 5-1, 15, 19, 25, 32, 33, 35, 36, 41, 

43, 46, 5% 51, 59-62, 65, 67, 72, 74, 

78-80, 85, 86, 88, 91, 94, 97, 100, 105, 

108, 112, 116 
Kenya, 6, 25, 41, 84, 110 



Korea, 19, 41, 59, 65, 86, 91, 97, 105 

Kuwait, 1, 45, 51, 74, 116 

Lebanon, 19, 86 

Luxembourg, 105 

Mexico, 6, 19, 25, 26, 41, 42, 44, 45, 58, 67, 

71, 74, 80, 82, 84, 86, 91, 97, 105, 106, 116 
Nepal, 105 

Netherlands, 19, 41, 59, 64, 65, 74, 80, 81, 

84-86, 96, 97, 105 
New Zealand, 7, 19, 41, 59, 65, 72, 91, 97, 105 
Nigeria, 1, 6, 19, 25, 41, 51, 65, 74, 81, 84, 86, 

88, 90, 105, 108, 116 
Norway, 19, 41, 52, 59, 89, 105 
Pakistan, 16, 22, 23, 25, 65, 81, 84, 105 
Panama, 11, 26, 27, 74, 81, 86, 115 
Peru, 6, 19, 41, 42, 44, 105 
Philippines, 6, 7, 41, 59, 86, 88, 105 
Poland, 3, 18, 19, 22-25, 29, 33, 35, 36, 41, 45, 

46, 52, 59, 65, 67, 68, 72, 74, 88, 97, 104, 

105 
Portugal, 28, 65, 105 
P.R.C., 29, 41, 46, 47, 1% 76, 93 
Romania, 18, 21, 22, 25, 59, 96 
Senegal, 25, 105 
Sierra Leone, 74, 81, 86, 105 
Singapore, 15, 108 

South Africa, 15, 41, 65, 67, 81, 86, 105, 108 
Spain, 19, 25, 41, 52, 65, 82, 105 
Sri Lanka, 41, 72, 82, 105 
Sudan, 19, 74, 82, 108 
Sweden, 2, 14-16, 18-20, 41, 52, 59, 63, 65-67, 

72, 74, 86, 89, 91, 97, 101, 105 
Switzerland, 18-21, 37, 39, 41, 59, 65, 67, 72, 

74, 85, 86, 97, 100, 101, 105, 108 
Tanzania, 41, 43 
Thailand, 41, 58, 62, 74, 76, 84 
Turkey, 41, 59, 72, 105 
U.S.S.R., 5, 18, 21, 22, 25, 28, 34-36, 41, 43, 

45, 46, 53-57, 61, 63, 71, 72, 82, 85, 86, 

94, 95, 100, 105, 107, 108, 116 
United Kingdom, 2, 19, 20, 41, 59, 62, 64-67, 

74, 84, 86, 103, 105, 107, 108, 1-7, 11, 

13-15, 19, 21-37, 39, 43, 45-50, 52-59, 

62-65, 68, 1% 71 
United States, 73, 74, 76, 80, 84, 85, 87-91, 

93, 94, 24, 99, 100, 103, 105, 107, 108, 

110, 115, 116 
Uruguay, 19, 41, 42, 44, 105 
Venezuela, 6, 25, 41, 42, 51, 7t^, 86, 105 
West Indies, 11, 19 
Yugoslavia, 18, 19, 21-23, 25, 41, 58, 64, 65, 

67, 72, 88, 97 
Zambia, 41 

Zimbabwe, 25, 65, 105 
Taiwan, 7, 15, 19, 41, 59, 86, 97, 105 



128 



Index by Research Area 



Aged, aging, 1, 7, 24, 52, 53, 58, 64, 70-72, 76, 
101 

Allergy and infectious diseases 
Allergy, 1, 20, 73, 76 
Communicable disease, 83 
Immunology, 16, 22, 23, 26, 30, 31, 33-35, 
37, 40, 56, 71, 74-78, 80, 82-85, 91, 
101 
Infectious disease, 23, 80, 83, 84, 101 

Arthritis and skeletal diseases, 5, 21, 61, 63 

Cancer, 1-5, 15, 16, 21, 23, 25, 27-44, 51, 72, 
76, 88, 93, 94 

Cardiovascular, pulmonary, and blood systems 
Anemia, including sickle cell anemia, 5, 

17, 59, 61 
Blood, 1, 4-6, 13, 15, 17, 19, 24, 27, 31, 

45-53, 55-60, 62, 64, 72, 81, 105, 107 
Cardiovascular/cardivascular disease, 1, 

5-1, 23, 25, 26, 45-53, 55, 57-59 
Coronary /coronary disease, 6, 7, 13, 45, 

46, 49-52, 54, 55, 57-53 
Heart, 1, 5-7, 13, 15, 45-47, 49-59 
Hypertension, 6, 7, 13, 23, 45-49, 51, 52, 

55-60, 64 
Lung, 1, 15, 28, 29, 32, 33, 43, 44, 45-47, 

60, 93, 96, 97 

Clinical trials, 31-33, 41, 43, 46, 59, 82, 101 

Dental/Oral health, 1, 90, 91 

Diabetes, 5, 17, 19-21, 59, 61, 63, 64 

Endocrinology, 14, 40, 63, 89 

Environmental health, including occupational 
health, 2, 23, 93-95 



Epidemiology, 15, 17, 25, 27, 29-32, 35, 37, 39, 
40, 43, 44, 47, 48, 53, 56, 59, 64, 73, 
77-79, 81, 82, 85, 88, 89, 101 

Eye/vision, including glaucoma, 2, 13, 15, 17, 
22, 24, 61, 62, 99-102 

Genetics, growth, and reproductive studies 
Child health, 7, 23, 87 
Family planning, 87 

Genetics, 5, 7, 16, 35, 40, 49, 51, 56, 64, 
72, 75, 76, 83, 87, 89, 91, 94, 95, 97, 
103 
Growth, 4, 16, 33, 38, 44, 54, 62, 87, 89, 93 
Human development, 7, 71, Z7 

Hepatic, renal, and digestive systems 
Digestive diseases, 61 
Kidney, 5, 19, 31, 61, 63, 64, 68, 72, 82, 

106 
Liver, 3-5, 29, 32, 34, 44, 65, 97 

Information sciences 

Information systems, 58, 66, 69, 82, 101 
Library, 24, 36, 37, 39, 66-69, 97, 112 

Metabolic diseases/metabolism, 30, 32, 50, 
53-55, 62-65, 72, 82, 96, 97 

Neurological disorders and stroke 
Epilepsy, 6, 104-106 
Neuroepidemiology, 6 
Neurological disorders, 104 
Stroke, 2, 6, 13, 50, 51, 59, 60, 104, 105 

Nutrition, 15, 29, 44, 45-47, 51, 59-62, 64, 71, 
87, 88, 90, 96, 99, 114 

Prevention, 1-3, 5, 13, 15, 24, 26, 28, 31-33, 
35, 37, 40, 43-47, 49, 51, 52, 54, 58, 64, 
73, 77, 78, 87, 90, 93, 99-102, 104 



liU.S. GOVERNMENT PRINTING OFFICE: 1983-38 1-132:3154 



129 



NIH Library, BvMma ]Ti 
National lnsl,,_ 
Bethesda, ftid. 20205" 



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